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Sample records for bystander effect observed

  1. Mechanisms of the Bystander Effect

    SciTech Connect

    Hall, Eric J.

    2008-07-15

    Generations of students in radiation biology have been taught that heritable biological damage requires direct damage to DNA. We now know that this is not true. The Bystander Effect is the name given to the phenomenon whereby biological effects are observed in cells that are not themselves traversed by a charged particle, but are in close proximity to cells that are. Several research groups have convincingly demonstrated a bystander effect for alpha particle, which are heavy and high LET, because charged particles can be focused into a tiny beam that can be directed onto individual cells. The biological effects seen in adjacent non-hit cells clearly represents a bystander effect. It is not so easy to demonstrate a similar effect for x-rays or for the electrons set in motion by the absorption of x-rays. In this project we used two types of cell that could be recognized one from the other. One cell type was fed radioactive tritiated thymidine, which is incorporated into the DNA, . The tritium emits electrons which have a very short range so that they do not even get out of the cell. These cells were then mixed with a different type of cell which are routinely used to assess mutations. The mixed cells formed a cluster, where the two types of cells were in close contact, and left for some hours. Subsequently, the two types of cells were separated and studied. A substantial fraction of the cells that had incorporated the tritiated thymidine were killed by the radiation. The interesting finding is that the cells that had not incorporated tritiated thymidine, but had been in close contact with cells that had, exhibited a significant incidence of mutations. These experiments clearly demonstrated a bystander effect for low LET electrons. In further experiments, it was possible to show that the bystander effect was greatest when the two cell types were in gap junction communication.

  2. A Bystander Effect Observed in Boron Neutron Capture Therapy: A Study of the Induction of Mutations in the HPRT Locus

    SciTech Connect

    Kinashi, Yuko . E-mail: kinashi@rri.kyoto-u.ac.jp; Masunaga, Shinichiro; Nagata, Kenji; Suzuki, Minoru; Takahashi, Sentaro; Ono, Koji

    2007-06-01

    Purpose: To investigate bystander mutagenic effects induced by {alpha}-particles during boron neutron capture therapy, we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, and cells that did not contain the boron compound. The BSH-containing cells were irradiated with {alpha}-particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were affected only by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. Methods and Materials: The lethality and mutagenicity measured by the frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase locus were examined in Chinese hamster ovary cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the resulting cell population. The molecular structures of the mutations were determined using multiplex polymerase chain reactions. Results: Because of the bystander effect, the frequency of mutations increased in the cells located nearby the BSH-containing cells compared with control cells. Molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were less than those induced by the original neutron irradiation. Conclusion: These results suggested that in boron neutron capture therapy, the mutations caused by the bystander effect and those caused by the original neutron irradiation are induced by different mechanisms.

  3. Neutron induced bystander effect among zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Ng, C. Y. P.; Kong, E. Y.; Kobayashi, A.; Suya, N.; Uchihori, Y.; Cheng, S. H.; Konishi, T.; Yu, K. N.

    2015-12-01

    The present paper reported the first-ever observation of neutron induced bystander effect (NIBE) using zebrafish (Danio rerio) embryos as the in vivo model. The neutron exposure in the present work was provided by the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. Two different strategies were employed to induce NIBE, namely, through directly partnering and through medium transfer. Both results agreed with a neutron-dose window (20-50 mGy) which could induce NIBE. The lower dose limit corresponded to the threshold amount of neutron-induced damages to trigger significant bystander signals, while the upper limit corresponded to the onset of gamma-ray hormesis which could mitigate the neutron-induced damages and thereby suppress the bystander signals. Failures to observe NIBE in previous studies were due to using neutron doses outside the dose-window. Strategies to enhance the chance of observing NIBE included (1) use of a mono-energetic high-energy (e.g., between 100 keV and 2 MeV) neutron source, and (2) use of a neutron source with a small gamma-ray contamination. It appeared that the NASBEE facility used in the present study fulfilled both conditions, and was thus ideal for triggering NIBE.

  4. Defining a Possible Low LET Bystander Effect

    SciTech Connect

    Charles R. Geard

    2009-05-04

    Current radiation protection guidelines assume a linear response to ionizing radiations down through doses where epidemiological studies provide very limited to no information as to the propriety of such assumptions. The bystander response is a non-targeted effect which might impact such guidelines. These studies while clearly affirming a bystander response for high LET radiations, do not provide such affirmation for environmentally relevant low dose, low LET radiations. Caution and further study are necessary before making judgements that could impact on current standards.

  5. Epigenetic bystander-like effects of stroke in somatic organs

    PubMed Central

    Kovalchuk, Anna; Lowings, Michael; Rodriguez-Juarez, Rocio; Muhammad, Arif; Ilnytskyy, Slava; Kolb, Bryan; Kovalchuk, Olga

    2012-01-01

    Clinical evidence suggests that stroke may lead to damage of somatic organs. This communication of damage is well-established in the case of exposure to genotoxic agents is termed a bystander effect. Genotoxic stress-induced bystander effects are epigenetically mediated. Here we investigated whether stroke causes epigenetic bystander-like effects in the liver, kidney and heart. We found a significant increase in the levels of H3K3 acetylation and H3K4 trimethylation, as well as a decrease in the H3K9 trimethylation in the kidney tissue of stroked rats. Furthermore, here we for the first time show changes in the gene and microRNA expression profile in the kidney tissues of stroked rats, as compared to intact control animals. Interestingly, the observed changes were somewhat similar to those reported earlier in kidney injury, inflammation, and acute renal failure. Our data explain the recent epidemiological evidence for the increased incidence of acute kidney injury post-stroke and provide an important roadmap for the future analysis of the mechanisms and cellular repercussions of the stroke-induced bystander-like effects in distal somatic organs. PMID:22466454

  6. Time-lapse microscopy studies of bystander effects induced by photosensitization

    NASA Astrophysics Data System (ADS)

    Chen, Yin-Chu; Redmond, Robert W.

    2006-02-01

    Reactive oxygen species (ROS) are involved in the pathogenesis of many critical diseases and are also utilized as cytotoxic agents in a variety of treatments for eradication of diseased tissue, including cancer. Oxidative stress ensues when the level of ROS in a system exceeds the antioxidant capacity. Oxidative stress can have local (direct) and long-range (bystander) effects in cells and tissue and this research was carried out to determine the spatial and temporal nature of the photosensitized bystander effect using time-lapse fluorescence microscopy. By initiating photosensitization in only a portion of the microscopic imaging field it was possible to differentiate direct from bystander effects in EMT-6 murine breast cancer cells in 6-well plates. Elevated ROS levels are seen immediately following photodynamic treatment in direct cells with a delayed increase in oxidative stress observed in bystander cells. Cytotoxicity is also seen at earlier times in direct cells and occurs in bystander cells in a delayed fashion. These studies confirm the existence of a bystander effect following photosensitization and implicate mediators capable of diffusing in an intercellular manner from directly photosensitized cells to bystander cells and also implicate increased oxidative stress as a mechanistic factor in generating damage in bystander cells.

  7. Brief report: The bystander effect in cyberbullying incidents.

    PubMed

    Machackova, Hana; Dedkova, Lenka; Mezulanikova, Katerina

    2015-08-01

    This study examined the bystander effect in cyberbullying. Using self-reported data from 257 Czech respondents who had witnessed a cyberbullying attack, we tested whether provided help decreased with increased number of other bystanders. We controlled for several individual and contextual factors, including empathy, social self-efficacy, empathic response to victimization, and relationship to the victim. Results showed that participants tend to help the victims more in incidents with only one or two other bystanders. We also found that, as in the "offline" realm, bystander effect is not linear: no significant differences were found between incidents with a moderate number (3-10) and a larger number of total bystanders. Our findings, thus, provide support for the presence of the bystander effect in cyberbullying. PMID:26070168

  8. Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells

    PubMed Central

    Faqihi, Fahime; Neshastehriz, Ali; Soleymanifard, Shokouhozaman; Shabani, Robabeh; Eivazzadeh, Nazila

    2015-01-01

    Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects. PMID:26160180

  9. Vincristine-induced bystander effect in human lymphocytes.

    PubMed

    Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara; Piaggi, Simona; Facioni, Maria Sole; Scarpato, Roberto

    2016-07-01

    Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5±1.41 at 6μM, 22±2.12 at 12μM or 28.25±5.13 at 15μM vs. a control value of 4.75±1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75±0.88 at 0.0μM, 27.25±2.30 at 0.4μM, 46.25±1.94 at 0.8μM, 98.25±7.25 at 1.6μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the bystander effect induced by VCR. In fact, we observed an increased level of ROS, IL-32 and TGF-β in the CM from VCR treated cultures, not present in MMC treated cultures. PMID:27050754

  10. Heavy-ion radiation induced bystander effect in mice

    NASA Astrophysics Data System (ADS)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  11. Bystander Effects During Synchrotron Imaging Procedures?

    SciTech Connect

    Schueltke, Elisabeth; Nikkhah, Guido; Bewer, Brian; Wysokinski, Tomasz; Chapman, Dean

    2010-07-23

    Using monochromatic beam and synchrotron phase-contrast technique at the biomedical beamline of the Italian synchrotron facility Elettra (SYRMEP), we have shown in a small animal model of malignant brain tumor that it is possible to obtain high-resolution images of very small tumors when they have developed from implanted tumor cells loaded with colloidal gold nanoparticles (GNP). All previous experiments were conducted in post-mortem samples. We have now designed a cell culture experiment to investigate the effects of synchrotron radiation with an energy and dose profile similar to that expected in our first in vivo imaging studies according to the protocol developed at SYRMEP.Materials and Methods: Culture flasks containing either gold-loaded or naieve C6 glioma cells were exposed to a dose of 0.5 Gy at 24 keV. The irradiated medium was aspirated and replaced with fresh growth medium. Twenty-four hours later this non-irradiated medium exposed to irradiated cells was aspirated, then added to non-irradiated C6 cells in order to investigate whether bystander effects are seen under the conditions of our image acquisition protocol. The irradiated medium was added to a number of other non-irradiated cell cultures. Cell counts were followed until 72 hrs after irradiation. Western blots were conducted with H2AX antibodies. This experiment was one of the first biomedical experiments conducted at BMIT, the new biomedical imaging and therapy beamline of the Canadian Light Source.Results: No significant differences in proliferation were seen between cells that were directly irradiated, exposed to irradiated medium or exposed to the non-irradiated 24-hr-medium from the irradiated cells. However, there was a tendency towards a higher number of double strand breaks in previously irradiated cells when they were exposed to non-irradiated medium that had been in contact with irradiated cells for 24 hrs.

  12. Bystander Effects During Synchrotron Imaging Procedures?

    NASA Astrophysics Data System (ADS)

    Schültke, Elisabeth; Bewer, Brian; Wysokinski, Tomasz; Chapman, Dean; Nikkhah, Guido

    2010-07-01

    Using monochromatic beam and synchrotron phase-contrast technique at the biomedical beamline of the Italian synchrotron facility Elettra (SYRMEP), we have shown in a small animal model of malignant brain tumor that it is possible to obtain high-resolution images of very small tumors when they have developed from implanted tumor cells loaded with colloidal gold nanoparticles (GNP). All previous experiments were conducted in post-mortem samples. We have now designed a cell culture experiment to investigate the effects of synchrotron radiation with an energy and dose profile similar to that expected in our first in vivo imaging studies according to the protocol developed at SYRMEP. Materials and Methods: Culture flasks containing either gold-loaded or naïve C6 glioma cells were exposed to a dose of 0.5 Gy at 24 keV. The irradiated medium was aspirated and replaced with fresh growth medium. Twenty-four hours later this non-irradiated medium exposed to irradiated cells was aspirated, then added to non-irradiated C6 cells in order to investigate whether bystander effects are seen under the conditions of our image acquisition protocol. The irradiated medium was added to a number of other non-irradiated cell cultures. Cell counts were followed until 72 hrs after irradiation. Western blots were conducted with H2AX antibodies. This experiment was one of the first biomedical experiments conducted at BMIT, the new biomedical imaging and therapy beamline of the Canadian Light Source. Results: No significant differences in proliferation were seen between cells that were directly irradiated, exposed to irradiated medium or exposed to the non-irradiated 24-hr-medium from the irradiated cells. However, there was a tendency towards a higher number of double strand breaks in previously irradiated cells when they were exposed to non-irradiated medium that had been in contact with irradiated cells for 24 hrs.

  13. Recursive mentalizing and common knowledge in the bystander effect.

    PubMed

    Thomas, Kyle A; De Freitas, Julian; DeScioli, Peter; Pinker, Steven

    2016-05-01

    The more potential helpers there are, the less likely any individual is to help. A traditional explanation for this bystander effect is that responsibility diffuses across the multiple bystanders, diluting the responsibility of each. We investigate an alternative, which combines the volunteer's dilemma (each bystander is best off if another responds) with recursive theory of mind (each infers what the others know about what he knows) to predict that actors will strategically shirk when they think others feel compelled to help. In 3 experiments, participants responded to a (fictional) person who needed help from at least 1 volunteer. Participants were in groups of 2 or 5 and had varying information about whether other group members knew that help was needed. As predicted, people's decision to help zigzagged with the depth of their asymmetric, recursive knowledge (e.g., "John knows that Michael knows that John knows help is needed"), and replicated the classic bystander effect when they had common knowledge (everyone knowing what everyone knows). The results demonstrate that the bystander effect may result not from a mere diffusion of responsibility but specifically from actors' strategic computations. (PsycINFO Database Record PMID:26913616

  14. The Mechanisms of Radiation-Induced Bystander Effect

    PubMed Central

    Najafi, M; Fardid, R; Hadadi, Gh; Fardid, M

    2014-01-01

    The radiation-induced bystander effect is the phenomenon which non-irradiated cells exhibit effects along with their different levels as a result of signals received from nearby irradiated cells. Responses of non-irradiated cells may include changes in process of translation, gene expression, cell proliferation, apoptosis and cells death. These changes are confirmed by results of some In-Vivo studies. Most well-known important factors affecting radiation-induced bystander effect include free radicals, immune system factors, expression changes of some genes involved in inflammation pathway and epigenetic factors. PMID:25599062

  15. I know what you did: The effects of interpersonal deviance on bystanders.

    PubMed

    Ferguson, Merideth; Barry, Bruce

    2011-01-01

    Using social information processing theory, we explore how interpersonally directed deviance affects work group members who observe or are aware of these insidious behaviors. In a field study, we find that indirect knowledge of work group member interpersonal deviance leads to subsequent interpersonal deviance of a focal individual. We also find that when work group cohesion is high, direct observation of deviance is more likely to result in subsequent bystander deviance. These findings add concretely to theory and research on the bystander effects of workplace deviance. PMID:21280946

  16. Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

    PubMed Central

    Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

  17. SR-FTIR Coupled with Principal Component Analysis Shows Evidence for the Cellular Bystander Effect.

    PubMed

    Lipiec, E; Bambery, K R; Lekki, J; Tobin, M J; Vogel, C; Whelan, D R; Wood, B R; Kwiatek, W M

    2015-07-01

    Synchrotron radiation-Fourier transform infrared (SR-FTIR) microscopy coupled with multivariate data analysis was used as an independent modality to monitor the cellular bystander effect. Single, living prostate cancer PC-3 cells were irradiated with various numbers of protons, ranging from 50-2,000, with an energy of either 1 or 2 MeV using a proton microprobe. SR-FTIR spectra of cells, fixed after exposure to protons and nonirradiated neighboring cells (bystander cells), were recorded. Spectral differences were observed in both the directly targeted and bystander cells and included changes in the DNA backbone and nucleic bases, along with changes in the protein secondary structure. Principal component analysis (PCA) was used to investigate the variance in the entire data set. The percentage of bystander cells relative to the applied number of protons with two different energies was calculated. Of all the applied quantities, the dose of 400 protons at 2 MeV was found to be the most effective for causing significant macromolecular perturbation in bystander PC-3 cells. PMID:26121225

  18. Studies of Bystander Effects in 3-D Tissue Systems Using a Low-LET Microbeam

    SciTech Connect

    Brenner, David J.

    2009-07-17

    It is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. Little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be important. Previous work demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. Additional studies were undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells were inactivated when cells were irradiated at high density than at low density. In addition, the oncogenic transformation frequency was significantly higher in high-density cultures. These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions. Additional studies to address the relationship between the bystander effect and the adaptive response were undertaken. A novel apparatus, where targeted and non-targeted cells were grown in close proximity, was used to investigate these. It was further examined whether a bystander effect or an adaptive response could be induced by a factor(s) present in the supernatants of cells exposed to a high or low dose of X-rays, respectively. When non-hit cells were co-cultured for 24 h with cells irradiated with 5 Gy alpha-particles, a significant increase in both cell killing and oncogenic transformation frequency was observed. If these cells were treated with 2 cGy X-rays 5 h before co-culture with irradiated cells, approximately 95% of the bystander effect was cancelled out. A 2.5-fold decrease in the oncogenic transformation

  19. The potential impact of bystander effects on radiation risks in a Mars mission

    NASA Technical Reports Server (NTRS)

    Brenner, D. J.; Elliston, C. D.; Hall, E. I. (Principal Investigator)

    2001-01-01

    Densely ionizing (high-LET) galactic cosmic rays (GCR) contribute a significant component of the radiation risk in free space. Over a period of a few months-sufficient for the early stages of radiation carcinogenesis to occur-a significant proportion of cell nuclei will not be traversed. There is convincing evidence, at least in vitro, that irradiated cells can send out signals that can result in damage to nearby unirradiated cells. This observation can hold even when the unirradiated cells have been exposed to low doses of low-LET radiation. We discuss here a quantitative model based on the a formalism, an approach that incorporates radiobiological damage both from a bystander response to signals emitted by irradiated cells, and also from direct traversal of high-LET radiations through cell nuclei. The model produces results that are consistent with those of a series of studies of the bystander phenomenon using a high-LET microbeam, with the end point of in vitro oncogenic transformation. According to this picture, for exposure to high-LET particles such as galactic cosmic rays other than protons, the bystander effect is significant primarily at low fluences, i.e., exposures where there are significant numbers of untraversed cells. If the mechanisms postulated here were applicable in vivo, using a linear extrapolation of risks derived from studies using intermediate doses of high-LET radiation (where the contribution of the bystander effect may be negligible) to estimate risks at very low doses (where the bystander effect may be dominant) could underestimate the true risk from low doses of high-LET radiation. It would be highly premature simply to abandon current risk projections for high-LET, low-dose radiation; however, these considerations would suggest caution in applying results derived from experiments using high-LET radiation at fluences above approximately 1 particle per nucleus to risk estimation for a Mars mission.

  20. The potential impact of bystander effects on radiation risks in a Mars mission.

    PubMed

    Brenner, D J; Elliston, C D

    2001-11-01

    Densely ionizing (high-LET) galactic cosmic rays (GCR) contribute a significant component of the radiation risk in free space. Over a period of a few months-sufficient for the early stages of radiation carcinogenesis to occur-a significant proportion of cell nuclei will not be traversed. There is convincing evidence, at least in vitro, that irradiated cells can send out signals that can result in damage to nearby unirradiated cells. This observation can hold even when the unirradiated cells have been exposed to low doses of low-LET radiation. We discuss here a quantitative model based on the a formalism, an approach that incorporates radiobiological damage both from a bystander response to signals emitted by irradiated cells, and also from direct traversal of high-LET radiations through cell nuclei. The model produces results that are consistent with those of a series of studies of the bystander phenomenon using a high-LET microbeam, with the end point of in vitro oncogenic transformation. According to this picture, for exposure to high-LET particles such as galactic cosmic rays other than protons, the bystander effect is significant primarily at low fluences, i.e., exposures where there are significant numbers of untraversed cells. If the mechanisms postulated here were applicable in vivo, using a linear extrapolation of risks derived from studies using intermediate doses of high-LET radiation (where the contribution of the bystander effect may be negligible) to estimate risks at very low doses (where the bystander effect may be dominant) could underestimate the true risk from low doses of high-LET radiation. It would be highly premature simply to abandon current risk projections for high-LET, low-dose radiation; however, these considerations would suggest caution in applying results derived from experiments using high-LET radiation at fluences above approximately 1 particle per nucleus to risk estimation for a Mars mission. PMID:11604082

  1. MiR-21 is involved in radiation-induced bystander effects

    PubMed Central

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication. PMID:25483031

  2. Effects of group status and victim sex on female bystanders' responses to a potential party rape.

    PubMed

    Katz, Jennifer; Colbert, Samuel; Colangelo, Liane

    2015-01-01

    This research examined bystander responses to 1 of 4 potential party rape scenarios. Undergraduate women (N = 249) imagined attending a party either alone or with three friends where a sober man led an intoxicated potential victim (either male or female) into a bedroom. After random assignment to conditions, participants reported on intent to help and barriers to helping the potential victim. In contrast to the classic bystander effect, bystanders in groups intended to offer more help than lone bystanders. Bystanders also intended to offer more help to potential female than male victims and experienced more barriers to helping male victims. Two of these barriers (lack of personal responsibility to help and identifying risk) explained the lower intentions to help potential male victims. Potential male victims were more likely than female victims to be perceived as gay, and bystanders reported the least intentions to help presumably gay men at risk. PMID:25929141

  3. Bystander effect in human hepatoma HepG2 cells caused by medium transfers at different times after high-LET carbon ion irradiation

    NASA Astrophysics Data System (ADS)

    Wu, Qingfeng; Li, Qiang; Jin, Xiaodong; Liu, Xinguo; Dai, Zhongying

    2011-01-01

    Although radiation-induced bystander effects have been well documented in a variety of biological systems, whether irradiated cells have the ability to generate bystander signaling persistently is still unclear and the clinical relevance of bystander effects in radiotherapy remains to be elucidated. This study examines tumor cellular bystander response to autologous medium from cell culture irradiated with high-linear energy transfer (LET) heavy ions at a therapeutically relevant dose in terms of clonogenic cell survival. In vitro experiments were performed using human hepatoma HepG2 cell line exposed to 100 keV/μm carbon ions at a dose of 2 Gy. Two different periods (2 and 12 h) after irradiation, irradiated cell conditioned medium (ICCM) and replenished fresh medium were harvested and then transferred to unirradiated bystander cells. Cellular bystander responses were measured with the different medium transfer protocols. Significant higher survival fractions of unirradiated cells receiving the media from the irradiated cultures at the different times post-irradiation than those of the control were observed. Even replenishing fresh medium for unirradiated cells which had been exposed to the ICCM for 12 h could not prevent the bystander cells from the increased survival fraction. These results suggest that the irradiated cells could release unidentified signal factor(s), which induced the increase in survival fraction for the unirradiated bystander cells, into the media sustainedly and the carbon ions triggered a cascade of signaling events in the irradiated cells rather than secreting the soluble signal factor(s) just at a short period after irradiation. Based on the observations in this study, the importance of bystander effect in clinical radiotherapy was discussed and incorporating the bystander effect into the current radiobiological models, which are applicable to heavy ion radiotherapy, is needed urgently.

  4. Low Doses of Gamma-Irradiation Induce an Early Bystander Effect in Zebrafish Cells Which Is Sufficient to Radioprotect Cells

    PubMed Central

    Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle

    2014-01-01

    The term “bystander effect” is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01–0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors. PMID:24667817

  5. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  6. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    PubMed Central

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  7. Rescue effects: irradiated cells helped by unirradiated bystander cells.

    PubMed

    Lam, R K K; Fung, Y K; Han, W; Yu, K N

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  8. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

  9. The use of radiation microbeams to investigate the bystander effect in cells and tissues

    NASA Astrophysics Data System (ADS)

    Folkard, M.; Prise, K. M.; Michette, A. G.; Vojnovic, B.

    2007-09-01

    Microbeams are ideally suited to the study of so-called 'non-targeted' phenomena that are now known to occur when living cells and tissues are irradiated. Non-targeted effects are those where cells are seen to respond to ionising radiation through pathways other than direct damage to the DNA. One such phenomenon is the 'bystander effect'; the observation that unirradiated cells can be damaged through signalling pathways initiated by a nearby irradiated cell. The effect leads to a highly non-linear dose-response at low doses and is forcing a rethink of established models used to estimate low-dose radiation risk, which are largely based on linear extrapolations from epidemiological data at much higher doses. The bystander effect may also provide an opportunity for improvements in the treatment of cancer by radiotherapy, as it may be possible to chemically influence the bystander response in such a way as to enhance cell killing in tumour cells or to protect healthy tissue.

  10. Are Epigenetic Mechanisms Involved in Radiation-Induced Bystander Effects?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2012-01-01

    The “non-targeted effects” of ionizing radiation including bystander effects and genomic instability are unique in that no classic mutagenic event occurs in the cell showing the effect. In the case of bystander effects, cells which were not in the field affected by the radiation show high levels of mutations, chromosome aberrations, and membrane signaling changes leading to what is termed “horizontal transmission” of mutations and information which may be damaging while in the case of genomic instability, generations of cells derived from an irradiated progenitor appear normal but then lethal and non-lethal mutations appear in distant progeny. This is known as “vertical transmission.” In both situations high yields of non-clonal mutations leading to distant occurrence of mutation events both in space and time. This precludes a mutator phenotype or other conventional explanation and appears to indicate a generalized form of stress-induced mutagenesis which is well documented in bacteria. This review will discuss the phenomenology of what we term “non-targeted effects,” and will consider to what extent they challenge conventional ideas in genetics and epigenetics. PMID:22629281

  11. Bystander effects in radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  12. A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

    PubMed Central

    Mothersill, C.; Moran, G.; McNeill, F.; Gow, M.D.; Denbeigh, J.; Prestwich, W.; Seymour, C.B.

    2007-01-01

    The induction of “bystander effects” i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy 60Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure. PMID:18648606

  13. Bystander Effects Induced by Medium From Irradiated Cells: Similar Transcriptome Responses in Irradiated and Bystander K562 Cells

    SciTech Connect

    Herok, Robert; Konopacka, Maria; Polanska, Joanna; Swierniak, Andrzej; Rogolinski, Jacek; Jaksik, Roman; Hancock, Ronald; Rzeszowska-Wolny, Joanna

    2010-05-01

    Purpose: Cells exposed to ionizing radiation release factors that induce deoxyribonucleic acid damage, chromosomal instability, apoptosis, and changes in the proliferation rate of neighboring unexposed cells, phenomena known as bystander effects. This work analyzes and compares changes in global transcript levels induced by direct irradiation and by bystander effects in K562 (human erythroleukemia) cells. Methods and Materials: Cells were X-irradiated with 4 Gy or transferred into culture medium collected from cells 1 h after irradiation (irradiation-conditioned medium). Global transcript profiles were assessed after 36 h of growth by use of Affymetrix microarrays (Affymetrix, Santa Clara, CA) and the kinetics of change of selected transcripts by quantitative reverse transcriptase-polymerase chain reaction. Results: The level of the majority (72%) of transcripts changed similarly (increase, decrease, or no change) in cells grown in irradiation-conditioned medium or irradiated, whereas only 0.6% showed an opposite response. Transcript level changes in bystander and irradiated cells were significantly different from those in untreated cells grown for the same amount of time and were confirmed by quantitative reverse transcriptase-polymerase chain reaction for selected genes. Signaling pathways in which the highest number of transcripts changed in both conditions were found in the following groups: neuroactive ligand-receptor, cytokine-cytokine receptor interaction, Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen-Activated Protein Kinase (MAPK) In control cells more transcripts were downregulated than in irradiated and bystander cells with transcription factors YBX1 and STAT5B, heat shock protein HSPA1A, and ribonucleic acid helicase DDX3X as examples. Conclusions: The transcriptomes of cells grown in medium from X-irradiated cells or directly irradiated show very similar changes. Signals released by irradiated cells may cause

  14. Membrane-Dependent Bystander Effect Contributes to Amplification of the Response to Alpha-Particle Irradiation in Targeted and Nontargeted Cells

    SciTech Connect

    Hanot, Maite; Hoarau, Jim; Carriere, Marie; Angulo, Jaime F.; Khodja, Hicham

    2009-11-15

    Purpose: Free radicals are believed to play an active role in the bystander response. This study investigated their origin as well as their temporal and spatial impacts in the bystander effect. Methods and Materials: We employed a precise alpha-particle microbeam to target a small fraction of subconfluent osteoblastic cells (MC3T3-E1). gammaH2AX-53BP1 foci, oxidative metabolism changes, and micronuclei induction in targeted and bystander cells were assessed. Results: Cellular membranes and mitochondria were identified as two distinct reactive oxygen species producers. The global oxidative stress observed after irradiation was significantly attenuated after cells were treated with filipin, evidence for the primal role of membrane in the bystander effect. To determine the membrane's impact at a cellular level, micronuclei yield was measured when various fractions of the cell population were individually targeted while the dose per cell remained constant. Induction of micronuclei increased in bystander cells as well as in targeted cells and was attenuated by filipin treatment, demonstrating a role for bystander signals between irradiated cells in an autocrine/paracrine manner. Conclusions: A complex interaction of direct irradiation and bystander signals leads to a membrane-dependent amplification of cell responses that could influence therapeutic outcomes in tissues exposed to low doses or to environmental exposure.

  15. Bystander effect induced by UV radiation; why should we be interested?

    PubMed

    Widel, Maria

    2012-01-01

    The bystander effect, whose essence is an interaction of cells directly subjected to radiation with adjacent non-subjected cells, via molecular signals, is an important component of ionizing radiation action. However, knowledge of the bystander effect in the case of ultraviolet (UV) radiation is quite limited. Reactive oxygen and nitrogen species generated by UV in exposed cells induce bystander effects in non-exposed cells, such as reduction in clonogenic cell survival and delayed cell death, oxidative DNA damage and gene mutations, induction of micronuclei, lipid peroxidation and apoptosis. Although the bystander effect after UV radiation has been recognized in cell culture systems, its occurrence in vivo has not been studied. However, solar UV radiation, which is the main source of UV in the environment, may induce in human dermal tissue an inflammatory response and immune suppression, events which can be considered as bystander effects of UV radiation. The oxidative damage to DNA, genomic instability and the inflammatory response may lead to carcinogenesis. UV radiation is considered one of the important etiologic factors for skin cancers, basal- and squamous-cell carcinomas and malignant melanoma. Based on the mechanisms of actions it seems that the UV-induced bystander effect can have some impact on skin damage (carcinogenesis?), and probably on cells of other tissues. The paper reviews the existing data about the UV-induced bystander effect and discusses a possible implication of this phenomenon for health risk.  PMID:23175338

  16. Spatio-temporal analysis of tamoxifen-induced bystander effects in breast cancer cells using microfluidics.

    PubMed

    Rios-Mondragon, Ivan; Wang, Xiang; Gerdes, Hans-Hermann

    2012-06-01

    The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy. PMID:23750189

  17. The role of protein kinase C alpha translocation in radiation-induced bystander effect

    PubMed Central

    Fang, Zihui; Xu, An; Wu, Lijun; Hei, Tom K.; Hong, Mei

    2016-01-01

    Ionizing radiation is a well known human carcinogen. Evidence accumulated over the past decade suggested that extranuclear/extracellular targets and events may also play a critical role in modulating biological responses to ionizing radiation. However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear. In the current study, AL cells were irradiated with alpha particles and responses of bystander cells were investigated. We found out that in bystander AL cells, protein kinase C alpha (PKCα) translocated from cytosol to membrane fraction. Pre-treatment of cells with PKC translocation inhibitor chelerythrine chloride suppressed the induced extracellular signal-regulated kinases (ERK) activity and the increased cyclooxygenase 2 (COX-2) expression as well as the mutagenic effect in bystander cells. Furthermore, tumor necrosis factor alpha (TNFα) was elevated in directly irradiated but not bystander cells; while TNFα receptor 1 (TNFR1) increased in the membrane fraction of bystander cells. Further analysis revealed that PKC activation caused accelerated internalization and recycling of TNFR1. Our data suggested that PKCα translocation may occur as an early event in radiation-induced bystander responses and mediate TNFα-induced signaling pathways that lead to the activation of ERK and up-regulation of COX-2. PMID:27165942

  18. Bystander effects and their implications for clinical radiation therapy: Insights from multiscale in silico experiments.

    PubMed

    Powathil, Gibin G; Munro, Alastair J; Chaplain, Mark A J; Swat, Maciej

    2016-07-21

    Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects, such as DNA mutation or bystander phenomena, may affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this paper, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model. PMID:27084360

  19. Proteomic overview and perspectives of the radiation-induced bystander effects.

    PubMed

    Chevalier, François; Hamdi, Dounia Houria; Saintigny, Yannick; Lefaix, Jean-Louis

    2015-01-01

    Radiation proteomics is a recent, promising and powerful tool to identify protein markers of direct and indirect consequences of ionizing radiation. The main challenges of modern radiobiology is to predict radio-sensitivity of patients and radio-resistance of tumor to be treated, but considerable evidences are now available regarding the significance of a bystander effect at low and high doses. This "radiation-induced bystander effect" (RIBE) is defined as the biological responses of non-irradiated cells that received signals from neighboring irradiated cells. Such intercellular signal is no more considered as a minor side-effect of radiotherapy in surrounding healthy tissue and its occurrence should be considered in adapting radiotherapy protocols, to limit the risk for radiation-induced secondary cancer. There is no consensus on a precise designation of RIBE, which involves a number of distinct signal-mediated effects within or outside the irradiated volume. Indeed, several cellular mechanisms were proposed, including the secretion of soluble factors by irradiated cells in the extracellular matrix, or the direct communication between irradiated and neighboring non-irradiated cells via gap junctions. This phenomenon is observed in a context of major local inflammation, linked with a global imbalance of oxidative metabolism which makes its analysis challenging using in vitro model systems. In this review article, the authors first define the radiation-induced bystander effect as a function of radiation type, in vitro analysis protocols, and cell type. In a second time, the authors present the current status of protein biomarkers and proteomic-based findings and discuss the capacities, limits and perspectives of such global approaches to explore these complex intercellular mechanisms. PMID:25795126

  20. Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

    SciTech Connect

    Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

    2008-05-07

    The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of {gamma}-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

  1. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

    PubMed Central

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-01-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects. PMID:24813621

  2. [Non-targeted effects (bystander, abscopal) of external beam radiation therapy: an overview for the clinician].

    PubMed

    Sun, R; Sbai, A; Ganem, G; Boudabous, M; Collin, F; Marcy, P-Y; Doglio, A; Thariat, J

    2014-12-01

    Radiotherapy is advocated in the treatment of cancer of over 50 % of patients. It has long been considered as a focal treatment only. However, the observation of effects, such as fatigue and lymphopenia, suggests that systemic effects may also occur. The description of bystander and abscopal effects suggests that irradiated cells may exert an action on nearby or distant unirradiated cells, respectively. A third type of effect that involves feedback interactions between irradiated cells was more recently described (cohort effect). This new field of radiation therapy is yet poorly understood and the definitions suffer from a lack of reproducibility in part due to the variety of experimental models. The bystander effect might induce genomic instability in non-irradiated cells and is thus extensively studied for a potential risk of radiation-induced cancer. From a therapeutic perspective, reproducing an abscopal effect by using a synergy between ionizing radiation and immunomodulatory agents to elicit or boost anticancer immune responses is an interesting area of research. Many applications are being developed in particular in the field of hypofractionated stereotactic irradiation of metastatic disease. PMID:25451674

  3. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    PubMed Central

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  4. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    PubMed

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  5. The Bystander-Effect: A Meta-Analytic Review on Bystander Intervention in Dangerous and Non-Dangerous Emergencies

    ERIC Educational Resources Information Center

    Fischer, Peter; Krueger, Joachim I.; Greitemeyer, Tobias; Vogrincic, Claudia; Kastenmuller, Andreas; Frey, Dieter; Heene, Moritz; Wicher, Magdalena; Kainbacher, Martina

    2011-01-01

    Research on bystander intervention has produced a great number of studies showing that the presence of other people in a critical situation reduces the likelihood that an individual will help. As the last systematic review of bystander research was published in 1981 and was not a quantitative meta-analysis in the modern sense, the present…

  6. Stochastic models of the bystander effect and of transmissible genomic instability: implications for mechanisms and low dose risks

    NASA Astrophysics Data System (ADS)

    Little, M. P.

    Bystander effects following exposure to α -particles have been observed in C3H 10T cells and in other experimental systems, and imply that linearly extrapolating low dose risks from high-dose data might materially underestimate risk. In many experimental systems there is evidence of saturation of dose response that would be expected from the bystander effect. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4 -- 4.0, with an upper 95% confidence limit of about 14. Assuming the bystander effect observed in the C3H 10T data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% confidence limit of about 7. As a consequence, the bystander effect observed in the C3H 10T system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α -particle exposure are surveyed; some of these data are more compatible with the epidemiological data. Three models of genomic instability recently developed by Little and Wright (Math. Biosci. 2003;183:111-34), with two, three and five stages, are compared with the four-stage model proposed by Luebeck and Moolgavkar (PNAS 2002;99:15095-100) and the two-stage model of Nowak et al. (PNAS 2002;99:16226-31). All models are fitted to SEER colon cancer data. Although the five-stage model of Little and Wright (2003) provides the best fit, it is not much superior to that of the model of Nowak et al. (2002) or the two- and three-stage models of Little and Wright (2003). The fit of the model of Luebeck and Moolgavkar (2002) is somewhat worse than these three, particularly for females under the age of 40. Comparison of the predictions of the two-stage models of Little and Wright (2003) and Nowak (2002) with patterns of excess risk in the Japanese atomic bomb

  7. Caspase-3-independent pathways proceeding in bystander effect of HSV-tk/GCV system

    NASA Astrophysics Data System (ADS)

    Lin, Juqiang; Ma, Yan; Zeng, Shaoqun; Zhang, Zhihong

    2008-02-01

    HSV-tk/GCV system, which is the virus-directed enzyme/prodrug therapy of herpes simplex virus (HSV) thymidine kinase (tk) gene / the anti-viral reagent ganciclovir (GCV), is one of the promising approaches in the rapidly growing area of gene therapy. As gene therapy of cancer such as suicide gene therapy has entered the clinic, another therapy effect which is called 'bystander effect' was reported. Bystander effect can lead to killing of non-transduced tumor cells in the immediate vicinity of GCV-treated HSV-TK-positive cells. Now the magnitude of 'bystander effect' is an essential factor for this anti-tumor approach in vivo. However, the mechanism which HSV-tk/ACV brings "bystander effect" is poorly understood. In this study, we monitor the activation of caspase-3 in HSV-tk/GCV system by a FRET probe CD3, a FRET-based indicator for activity of caspase3, which is composed of an enhanced cyan fluorescent protein, a caspase-sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. Through application of CD3 we have visualized the activation of caspase-3 in tk gene positive human adenoid cystic carcinoma (ACC-M) cells but not in bystander effect of HSV-tk/GCV system induced by GCV. This finding provides needed information for understanding the mechanisms by which suicide gene approaches actually kill cancer cells, and may prove to be helpful for the clinical treatment of cancers.

  8. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    PubMed

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling. PMID:27025606

  9. Bystander Activation and Anti-Tumor Effects of CD8+ T Cells Following Interleukin-2 Based Immunotherapy Is Independent of CD4+ T Cell Help

    PubMed Central

    Grossenbacher, Steven K.; Hsiao, Hui-Hua; Zamora, Anthony E.; Mirsoian, Annie; Koehn, Brent; Blazar, Bruce R.; Weiss, Jonathan M.; Wiltrout, Robert H.; Sckisel, Gail D.; Murphy, William J.

    2014-01-01

    We have previously demonstrated that immunotherapy combining agonistic anti-CD40 and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of highly cytolytic, antigen-independent “bystander-activated” (CD8+CD44high) T cells displaying a CD25−NKG2D+ phenotype in a cytokine dependent manner, which were responsible for the anti-tumor effects. While much attention has focused on CD4+ T cell help for antigen-specific CD8+ T cell expansion, little is known regarding the role of CD4+ T cells in antigen-nonspecific bystander-memory CD8+ T cell expansion. Utilizing CD4 deficient mouse models, we observed a significant expansion of bystander-memory T cells following IT which was similar to the non-CD4 depleted mice. Expanded bystander-memory CD8+ T cells upregulated PD-1 in the absence of CD4+ T cells which has been published as a hallmark of exhaustion and dysfunction in helpless CD8+ T cells. Interestingly, compared to CD8+ T cells from CD4 replete hosts, these bystander expanded cells displayed comparable (or enhanced) cytokine production, lytic ability, and in vivo anti-tumor effects suggesting no functional impairment or exhaustion and were enriched in an effector phenotype. There was no acceleration of the post-IT contraction phase of the bystander memory CD8+ response in CD4-depleted mice. The response was independent of IL-21 signaling. These results suggest that, in contrast to antigen-specific CD8+ T cell expansion, CD4+ T cell help is not necessary for expansion and activation of antigen-nonspecific bystander-memory CD8+ T cells following IT, but may play a role in regulating conversion of these cells from a central memory to effector phenotype. Additionally, the expression of PD-1 in this model appears to be a marker of effector function and not exhaustion. PMID:25119341

  10. Role of nitric oxide in the radiation-induced bystander effect.

    PubMed

    Yakovlev, Vasily A

    2015-12-01

    Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. PMID:26355395

  11. Genomic instability and bystander effects: a paradigm shift in radiation biology?

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2002-01-01

    A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

  12. Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

    PubMed Central

    Akudugu, John M.; Azzam, Edouard I.; Howell, Roger W.

    2013-01-01

    Purpose This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with 125I-labeled 5-iodo-2′-deoxyuridine (125IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold. Cultures were pulse-labeled for 3 h with 125IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2′-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT® EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with 125IdU/EdU. Additional aliquots were used to determine the mean 125I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA-MB-231 cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions These studies demonstrate the capacity of 125IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype. PMID:22489958

  13. Leverage Between the Buffering Effect and the Bystander Effect in Social Networking.

    PubMed

    Chiu, Yu-Ping; Chang, Shu-Chen

    2015-08-01

    This study examined encouraged and inhibited social feedback behaviors based on the theories of the buffering effect and the bystander effect. A system program was used to collect personal data and social feedback from a Facebook data set to test the research model. The results revealed that the buffering effect induced a positive relationship between social network size and feedback gained from friends when people's social network size was under a certain cognitive constraint. For people with a social network size that exceeds this cognitive constraint, the bystander effect may occur, in which having more friends may inhibit social feedback. In this study, two social psychological theories were applied to explain social feedback behavior on Facebook, and it was determined that social network size and social feedback exhibited no consistent linear relationship. PMID:26196410

  14. Influence of Exercise on Inflammation in Cancer: Direct Effect or Innocent Bystander?

    PubMed

    Murphy, E Angela; Enos, Reilly T; Velázquez, Kandy T

    2015-07-01

    We propose the hypothesis that the benefits of exercise on inflammation in cancer are a result of a direct effect on inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein 1, that are critical for cancer growth as well as a bystander effect of the established relationship between exercise and cancer. PMID:25906430

  15. Radiation-Induced Bystander Effects in A549 Cells Exposed to 6 MV X-rays.

    PubMed

    Yang, Shuning; Xu, Jing; Shao, Weixian; Geng, Chong; Li, Jia; Guo, Feng; Miao, Hui; Shen, Wenbin; Ye, Tao; Liu, Yazhou; Xu, Haiting; Zhang, Xuguang

    2015-07-01

    The aim of the study is to explore the bystander effects in A549 cells that have been exposed to 6MV X-ray. Control group, irradiated group, irradiated conditioned medium (ICM)-received group, and fresh medium group were designed in this study. A549 cells in the logarithmic growth phase were irradiated with 6MV X-ray at 0, 0.5, 1, 1.5, and 2. In ICM-received group, post-irradiation A549 cells were cultured for 3 h and were transferred into non-irradiated A549 cells for further cultivation. Clone forming test was applied to detect the survival fraction of cells. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of A549 cells 24, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation, and the curves of apoptosis were drawn. The changes in the cell cycles 4, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation were detected using PI staining flow cytometry. With the increase of irradiation dose, the survival fraction of A549 cells after the application of 0.5 Gy irradiation was decreasing continuously. In comparison to the control group, the apoptosis rate of the ICM-received group was increased in a time-dependent pattern, with the highest apoptosis rate observed at 72 h (p < 0.05). Cell count in G2/M stages was obviously increased compared with that of the control group (p < 0.05), with the highest count observed at 72 h, after which G2/M stage arrest was diminished. ICM can cause apparent A549 cell damage, indicating that 6MV X-ray irradiation can induce bystander effect on A549 cells, which reaches a peak at 72 h. PMID:25686868

  16. A Meta-Analysis of School-Based Bullying Prevention Programs' Effects on Bystander Intervention Behavior

    ERIC Educational Resources Information Center

    Polanin, Joshua R.; Espelage, Dorothy L.; Pigott, Therese D.

    2012-01-01

    This meta-analysis synthesized bullying prevention programs' effectiveness at increasing bystander intervention in bullying situations. Evidence from 12 school-based programs, involving 12,874 students, indicated that overall the programs were successful (Hedges's g = 0.20, 95% confidence interval [CI] = 0.11 to 0.29, p = 0.001), with larger…

  17. BYSTANDER EFFECTS GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIAION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    R. Julian Preston
    Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, N.C. 27711, USA

    There ...

  18. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  19. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  20. Bystander effects of ionizing radiation can be modulated by signaling amines

    SciTech Connect

    Poon, R.C.C.; Agnihotri, N.; Seymour, C.; Mothersill, C.

    2007-10-15

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca{sup 2+} ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects.

  1. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy). PMID:27602316

  2. Induction of a bystander mutagenic effect of alpha particles in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Vannais, D.; Hall, E. J.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

    2000-01-01

    Ever since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

  3. Induction of DNA Double-Strand Breaks and Cellular Migration Through Bystander Effects in Cells Irradiated With the Slit-Type Microplanar Beam of the Spring-8 Synchrotron

    SciTech Connect

    Kashino, Genro Kondoh, Takeshi; Nariyama, Nobuteru; Umetani, Keiji; Ohigashi, Takuji; Shinohara, Kunio; Kurihara, Ai; Fukumoto, Manabu; Tanaka, Hiroki; Maruhashi, Akira; Suzuki, Minoru; Kinashi, Yuko; Liu Yong; Masunaga, Shin-ichiro; Watanabe, Masami; Ono, Koji

    2009-05-01

    Purpose: To determine whether glioma cells irradiated with a microplanar X-ray beam exert bystander effects. Methods and Materials: Microplanar beam irradiation of glioma cells in vitro was done using the SPring-8 synchrotron radiation facility. The amount of DNA double-strand breaks (dsbs) was measured by the fluorescence intensity of phosphorylated H2AX or the number of 53BP1 foci. The dose distribution in a cell population exposed to a single microplanar beam was determined by the amount of phosphorylated H2AX-positive cells. Bystander effects were determined by counting the number of 53BP1 foci in nonirradiated cells treated with conditioned medium from cultures of irradiated cells. Results: More DNA dsbs were detected in cells adjacent to an area irradiated by the single beam than in cells in distant, nonirradiated areas as a result of bystander effects caused by scattered X-rays and DNA dsbs. In support of this, more 53BP1 foci were observed in nonirradiated, conditioned medium-treated cells than in control cells (i.e., cells not treated with irradiation or conditioned medium). These results suggest that DNA dsbs were induced in nonirradiated cells by soluble factors in the culture medium. In addition, we observed cellular migration into areas irradiated with peak doses, suggesting that irradiated cells send signals that cause nonirradiated cells to migrate toward damaged cells. Conclusions: Bystander effects are produced by factors secreted as a result of slit-type microplanar X-ray beam irradiation.

  4. LET-Dependent Bystander Effects Caused by Irradiation of Human Prostate Carcinoma Cells with X Rays or Alpha Particles

    PubMed Central

    Anzenberg, Vered; Chandiramani, Sarika; Coderre, Jeffrey A.

    2014-01-01

    Radiation-induced bystander effects have been demonstrated in both normal and tumor cells using a variety of different radiation qualities. Literature reports are contradictory, however, on whether there is an LET dependence of the bystander effect. This study investigated the ability of DU-145 human prostate carcinoma cells irradiated with either α particles or 250 kVp X rays to cause medium-mediated bystander effects in unirradiated populations of DU-145 cells or in AG01522 human fibroblasts. The end points measured in both of the bystander cell lines were micronucleus formation, γ-H2AX focus induction, and the surviving fraction. The incidence of micronuclei increased 1.5–2.0-fold in both tumor and fibroblast bystander cells after 4 h of co-culture with DU-145 tumor cells that had been directly irradiated with either α particles or X rays. Only the AG01522 fibroblasts showed bystander effects for the γ-H2AX focus (a 1.5-fold increase) and surviving fraction (a decrease to 0.8) end points when co-cultured with X-irradiated tumor cells. Alpha-particle irradiation of DU-145 tumor cells produced no decrease in the surviving fraction and no increase in γ-H2AX focus induction in co-cultured bystander cells of either cell line. These results indicate that there are LET-dependent differences in the signal released from DU-145 human prostate carcinoma cells and that, for some end points, bystander AG01522 fibroblasts and bystander DU-145 prostate carcinoma cells respond differently to the same medium-mediated signal. PMID:19024654

  5. Radiation induced bystander effect by GAP junction channels in human fibroblast cell

    NASA Astrophysics Data System (ADS)

    Furusawa, Y.; Shao, C.; Aoki, M.; Kobayashi, Y.; Funayama, T.; Ando, K.

    The chemical factor involved in bystander effect and its transfer pathway were investigated in a confluent human fibroblast cell (AG1522) population. Micronuclei (MN) and G1-phase arrest were detected in cells irradiated by carbon (~100 keV/μm) ions at HIMAC. A very low dose irradiation showed a high effectiveness in producing MN, suggesting a bystander effect. This effectiveness was enhanced by 8-Br-cAMP treatment that increases gap junctional intercellular communication (GJIC). On the other hand, the effect was reduced by 5% DMSO treatment, which reduce the reactive oxygen species (ROS), and suppressed by 100 μM lindane treatment, an inhibitor of GJIC. In addition, the radiation-induced G1-phase arrest was also enhanced by cAMP, and reduced or suppressed by DMSO or lindane. A microbeam device (JAERI) was also used for these studies. It was found that exposing one single cell in a confluent cell population to exactly one argon (~1260 keV/μm) or neon (~430 keV/ μm) ion, additional MN could be detected in many other unirradiated cells. The yield of MN increased with the number of irradiated cells. However, there was no significant difference in the MN induction when the cells were irradiated by increasing number of particles. MN induction by bystander effect was partly reduced by DMSO, and effectively suppressed by lindane. Our results obtained from both random irradiation and precise numbered irradiation indicate that both GJIC and ROS contributed to the radiation-induced bystander effect, but the cell gap junction channels likely play an essential role in the release and transfer of radiation-induced chemical factors.

  6. The induction of bystander mutagenic effects in vivo by alpha-particle irradiation in whole Arabidopsis thaliana plants.

    PubMed

    Li, Fanghua; Liu, Ping; Wang, Ting; Bian, Po; Wu, Yuejin; Wu, Lijun; Yu, Zengliang

    2010-08-01

    Our previous studies demonstrated distant/abscopal bystander effects in A. thaliana seeds and embryos; the postembryonic development of bystander tissues, such as root hair differentiation, primary root elongation, lateral root initiation and survival, were inhibited significantly by localized irradiation with microbeam protons and low-energy ions. In the present study, we further investigated radiation-induced bystander mutagenic effects in vivo in A. thaliana plants using homologous recombination (HR) and the expression level of the HR-related AtRAD54 gene as mutagenic end points. We found that alpha-particle irradiation of distal primary roots of young seedlings resulted in a significant increase in the frequency of HR in the aerial plants; the increased induction of HR occurred in every true leaf over the course of rosette development. Moreover, we also found that localized alpha-particle irradiation of roots induced a short-term up-regulated expression of the HR-related AtRAD54 gene in the nonirradiated aerial plants. These results suggested the existence of bystander mutagenic effects in vivo in plants. Treatment with the ROS scavenger DMSO dramatically reduced the effects of localized root irradiation on the induction of HR and expression of the AtRAD54 gene in bystander tissues, suggesting that ROS play a critical role in mediating the bystander mutagenic effects in plants. PMID:20681789

  7. A Heterotypic Bystander Effect for Tumor Cell Killing after AAVP-mediated Vascular-targeted Suicide Gene Transfer

    PubMed Central

    Trepel, Martin; Stoneham, Charlotte A.; Eleftherohorinou, Hariklia; Mazarakis, Nicholas D.; Pasqualini, Renata; Arap, Wadih; Hajitou, Amin

    2009-01-01

    Suicide gene transfer is the most commonly used cytotoxic approach in cancer gene therapy; however, a successful suicide gene therapy depends on the generation of efficient targeted systemic gene delivery vectors. We recently reported that selective systemic delivery of suicide genes such as the herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells via a novel targeted AAVP vector leads to suppression of tumor growth. This marked effect has been postulated to result primarily from the death of cancer cells by hypoxia following the targeted disruption of tumor blood vessels. Here we investigated whether an additional mechanism of action is involved. We show that there is a heterotypic bystander effect between endothelial cells expressing the HSVtk suicide gene and tumor cells. Treatment of co-cultures of HSVtk-transduced endothelial cells and non-HSVtk-transduced tumor cells with ganciclovir results in the death of both endothelial and tumor cells. Blocking of this effect by 18α-glycyrrhetinic acid indicates that gap junctions between endothelial and tumor cells are largely responsible for this phenomenon. Moreover, the observed bystander killing is mediated by connexin (Cx)43 and Cx26, which are expressed in both endothelial and tumor cell types. Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into host-derived tumor vascular endothelium. These findings add an alternative non-mutually exclusive and potentially synergistic cytotoxic mechanism to cancer gene therapy based on targeted AAVP, and further support the promising role of non-malignant tumor stromal cells as therapeutic targets. PMID:19671758

  8. Radiation-induced bystander effect and adaptive response in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Hei, T. K.

    2004-01-01

    Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  9. Bystander/abscopal effects induced in intact Arabidopsis seeds by low-energy heavy-ion radiation.

    PubMed

    Yang, Gen; Mei, Tao; Yuan, Hang; Zhang, Weiming; Chen, Lianyun; Xue, Jianming; Wu, Lijun; Wang, Yugang

    2008-09-01

    To date, radiation-induced bystander effects have been observed largely in in vitro single-cell systems; verification of both the effects and the mechanisms in multicellular systems in vivo is important. Previously we showed that bystander/ abscopal effects can be induced by irradiating the shoot apical meristem cells in Arabidopsis embryos. In this study, we investigated the in vivo effects induced by 30 keV 40Ar ions in intact Arabidopsis seeds and traced the postembryonic development of both irradiated and nonirradiated shoot apical meristem and root apical meristem cells. Since the range of 30 keV 40Ar ions in water is about 0.07 microm, which is less than the distance from the testa to shoot apical meristem and root apical meristem in Arabidopsis seeds (about 100 microm), the incident low-energy heavy ions generally stop in the proximal surface. Our results showed that, after the 30 keV 40Ar-ion irradiation of shielded and nonshielded Arabidopsis seeds at a fluence of 1.5 x 10(17) ions/cm2, short- and long-term postembryonic development, including germination, root hair differentiation, primary root elongation, lateral root initiation and survival, was significantly inhibited. Since shoot apical meristem and root apical meristem cells were not damaged directly by radiation, the results suggested that a damage signal(s) is transferred from the irradiated cells to shoot apical meristem and root apical meristem cells and causes the ultimate developmental alterations, indicating that long-distance bystander/ abscopal effects exist in the intact seed. A further study of mechanisms showed that the effects are associated with either enhanced generation of reactive oxygen species (ROS) or decreased auxin-dependent transcription in postembryonic development. Treatment with the ROS scavenger dimethyl sulfoxide (DMSO) or synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) can significantly reverse both the alterations in postembryonic development and auxin

  10. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    PubMed

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. PMID:26653982

  11. Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

    NASA Astrophysics Data System (ADS)

    He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

    2014-04-01

    High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

  12. Cancer Stem Cells Protect Non-Stem Cells From Anoikis: Bystander Effects.

    PubMed

    Kim, Seog-Young; Hong, Se-Hoon; Basse, Per H; Wu, Chuanyue; Bartlett, David L; Kwon, Yong Tae; Lee, Yong J

    2016-10-01

    Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non-stem cells is crucial for developing a novel cancer therapy. We used CSC-like and non-stem breast cancer MDA-MB-231 and MDA-MB-453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E-cadherin)-extracellular signal-regulated kinase (Erk) axis in anoikis. Data from E-cadherin small hairpin RNA assay and mitogen-activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E-cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC-like cells, increased secretion of interleukin-6 (IL-6) and growth-related oncogene (Gro) chemokines was detected during mammosphere culture in non-stem cells. Similar results were observed in mixed cells. Interestingly, CSC-like cells protected non-stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC-like cells and non-stem cells. J. Cell. Biochem. 117: 2289-2301, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918647

  13. The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

    SciTech Connect

    Brenner, David J.

    2009-07-22

    Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

  14. Antioxidant enzymes and the mechanism of the bystander effect induced by ultraviolet C irradiation of A375 human melanoma cells.

    PubMed

    Ghosh, Rita; Guha, Dipanjan; Bhowmik, Sudipta; Karmakar, Sayantani

    2013-09-18

    Irradiated cells generate dynamic responses in non-irradiated cells; this signaling phenomenon is known as the bystander effect (BE). Factors secreted by the irradiated cells communicate some of these signals. Conditioned medium from UVC-irradiated A375 human melanoma cells was used to study the BE. Exposure of cells to conditioned medium induce cell-cycle arrest at the G2/M transition. Although conditioned medium treatment, by itself, did not alter cell viability, treated cells were more resistant to the lethal action of UVC or H2O2. This protective effect of conditioned medium was lost within 8h. Apoptotic or autophagic cell death was not involved in this resistance. Exposure to conditioned medium did not influence the rate of DNA repair, as measured by NAD(+) depletion. The activities of catalase and superoxide dismutase were elevated in cells exposed to conditioned medium, but returned to normal levels by 8h post-treatment. These results indicate a close correlation between BE-stimulated antioxidant activity and cellular sensitivity. Cell-cycle arrest and stimulation of antioxidant activity may account for the resistance to killing that was observed in bystander cells exposed to UVC or H2O2 treatment and are consistent with the role of the BE as a natural defense function triggered by UVC irradiation. PMID:23845763

  15. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  16. Tissue-Sparing Effect of X-ray Microplanar Beams Particulary in the CNS: Is a Bystander Effect Involved?

    SciTech Connect

    Dilmanian,A.; Qu, Y.; Feinendegen, L.; Pena, L.; Bacarian, T.; Henn, F.; Kalef-Ezra, J.; Liu, S.; Zhong, Z.; McDonald, J.

    2007-01-01

    Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of bystander effects in these repairs.

  17. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect.

    PubMed

    Tong, Liping; Yu, K N; Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi; Han, Wei

    2014-01-01

    Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after α-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor β1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy. PMID:24333162

  18. [Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation].

    PubMed

    Ermakov, A V; Kon'kova, M S; Kostiuk, S V; Smirnova, T D; Kameneva, L V; Veĭko, R V; Kubasova, I Iu; Liubchenko, L N; Veĭko, N N

    2010-01-01

    Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes. All these data indicate the existence of universal reaction of homological chromosome loci transposition which was revealed during AR development in differentiated (lymphocytes) and non-differentiated (hMSCs) and also it shows possibility of radiational BE development in suspension and monolayer cell cultures upon addition of stress-signalization factors in incubation medium. We suppose that these factors are extracellular genome DNA fragments apoptotic cells. PMID:20297680

  19. Dependence of the bystander effect for micronucleus formation on dose of heavy-ion radiation in normal human fibroblasts.

    PubMed

    Matsumoto, Yoshitaka; Hamada, Nobuyuki; Aoki-Nakano, Mizuho; Funayama, Tomoo; Sakashita, Tetsuya; Wada, Seiichi; Kakizaki, Takehiko; Kobayashi, Yasuhiko; Furusawa, Yoshiya

    2015-09-01

    Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV µm(-1)), neon (375 keV µm(-1)) and argon ions (1260 keV µm(-1)) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1-6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose. PMID:26242975

  20. Characterization of a bystander effect induced by the endocrine-disrupting chemical 6-propyl-2-thiouracil in zebrafish embryos.

    PubMed

    Liu, Chunsheng; Yan, Wei; Zhou, Bingsheng; Guo, Yongyong; Liu, Hongling; Yu, Hongxia; Giesy, John P; Wang, Jianghua; Li, Guangyu; Zhang, Xiaowei

    2012-08-15

    This study was conducted to evaluate possible bystander effects induced by the model chemical 6-propyl-2-thiouracil (PTU) on melanin synthesis. Zebrafish (Danio rerio) embryos were treated with PTU by either microinjection exposure, via waterborne exposure or indirectly through bystander exposure. Melanin content, related mRNA and protein expression were examined at the end of exposure (36 h post-fertilization). Direct exposure to PTU decreased the melanin content, up-regulated mRNA expressions of oculocutaneous albinism type 2 (OCA2), tyrosinase (TYR), dopachrometautomerase (DCT), tyrosinase-related protein 1 (TYRP1) and silver (SILV), and increased the protein expressions of TYR and SILV. Bystander exposure also up-regulated mRNA and protein expressions of TYR and SILV but increased melanin contents. Correlation analysis demonstrated that mRNA expressions of OCA2, TYR, DCT, TYRP1, SILV and protein expressions of TYR and SILV in bystander exposure groups were positively correlated with corresponding expressions in microinjection exposure groups. The results might have environmental implications and highlight the need to consider the bystander effects when assessing potential risks of endocrine-disrupting chemicals. PMID:22542736

  1. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

  2. Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Brooks, A. L.; Chatterjee, A. (Principal Investigator)

    2001-01-01

    Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

  3. Characteristics and mechanisms of the bystander response in monolayer cell cultures exposed to very low fluences of alpha particles

    NASA Astrophysics Data System (ADS)

    Little, John B.; Azzam, Edouard I.; de Toledo, Sonia M.; Nagasawa, Hatsumi

    2005-02-01

    When confluent cultures of mammalian cells are irradiated with very low fluences of alpha particles whereby only occasional cells receive any radiation exposure, genetic changes are observed in the non-irradiated ("bystander") cells. Upregulation of the p53 damage-response pathway as well as activation of proteins in the MAPK family occurred in bystander cells; p53 was phosphorylated on the serine 15 residue suggesting that the upregulation of p53 was a consequence of DNA damage. Damage signals were transmitted to bystander cells through gap junctions, as confirmed by the use of genetically manipulated cells including connexin43 knockouts. Expression of connexin43 was markedly enhanced by irradiation. A moderate bystander effect was observed for specific gene mutations and chromosomal aberrations. This effect was markedly enhanced in cells defective in the non-homologous end joining DNA repair pathway. Finally, an upregulation of oxidative metabolism occurred in bystander cells; the increased levels of reactive oxygen species appeared to be derived from flavine-containing oxidase enzymes. We hypothesize that genetic effects observed in non-irradiated bystander cells are a consequence of oxidative base damage; >90% of mutations in bystander cells were point mutations. When bystander cells cannot repair DNA double strand breaks, they become much more sensitive to the induction of chromosomal aberrations and mutations, the latter consisting primarily of deletion mutants. While we propose that the genetic effects occurring in bystander cells are a consequence of oxidative stress, the nature of the signal that initiates this process remains to be determined.

  4. Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

    PubMed Central

    Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

    2014-01-01

    Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

  5. Radiation-induced bystander effects and the DNA paradigm: an "out of field" perspective.

    PubMed

    Mothersill, Carmel; Seymour, C B

    2006-05-11

    Over the past 20 years there has been increasing evidence that cells and the progeny of cells surviving a very low dose of ionizing radiation [micro-mGy] can exhibit a wide range of non-monotonic effects such as adaptive responses, low dose hypersensitivity and other delayed effects. These effects are inconsistent with the expected dose-response, when based on extrapolation of high dose data and cast doubt on the reliability of extrapolating from high dose data to predict low dose effects. Recently the cause of many of these effects has been tentatively ascribed to so-called "bystander effects". These are effects that occur in cells not directly hit by an ionizing track but which are influenced by signals from irradiated cells and are thus highly relevant in situations where the dose is very low. Not all bystander effects may be deleterious although most endpoints measured involve cell damage or death. In this commentary, we consider how these effects impact the historical central dogma of radiobiology and radiation protection, which is that DNA double strand breaks are the primary radiation-induced lesion which can be quantifiably related to received dose and which determine the probability that a cancer will result from a radiation exposure. We explore the low dose issues and the evidence and conclude that in the very low dose region, the primary determinant of radiation exposure outcome is the genetic and epigenetic background of the individual and not solely the dose. What this does is to dissociate dose from effect as a quantitative relationship, but it does not necessarily mean that the effect is ultimately unrelated to DNA damage. The fundamental thesis we present is that at low doses fundamentally different mechanisms underlie radiation action and that at these doses, effect is not quantitatively related to dose. PMID:16414088

  6. Bystander Effects Induced by Continuous Low-Dose-Rate {sup 125}I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

    SciTech Connect

    Chen, H.H. Jia, R.F.; Yu, L.; Zhao, M.J.; Shao, C.L.; Cheng, W.Y.

    2008-12-01

    Purpose: To investigate bystander effects of low-dose-rate (LDR) {sup 125}I seed irradiation on human lung cancer cells in vitro. Methods and Materials: A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR {sup 125}I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), {gamma}H2AX foci, and apoptosis were assayed. Results: After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with {sup 125}I seed irradiated cells for 24 hours, MFR and the mean number of {gamma}H2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p <0.05), although they did not increase with irradiation dose. However, the proportion of bystander NCI-H446 cells with MN numbers {>=}3 and {gamma}H2AX foci numbers 15-19 and 20-24 was higher than that of bystander A549 cells. In addition, dimethyl sulfoxide (DMSO) treatment could completely suppress the bystander MN of NCI-H446 cells, but it suppressed only partly the bystander MN of A549 cells, indicating that reactive oxygen species are involved in the bystander response to NCI-H446 cells, but other signaling factors may contribute to the bystander response of A549 cells. Conclusions: Continuous LDR irradiation of {sup 125}I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes.

  7. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  8. Use of synchrotron medical microbeam irradiation to investigate radiation-induced bystander and abscopal effects in vivo.

    PubMed

    Fernandez-Palomo, Cristian; Bräuer-Krisch, Elke; Laissue, Jean; Vukmirovic, Dusan; Blattmann, Hans; Seymour, Colin; Schültke, Elisabeth; Mothersill, Carmel

    2015-09-01

    The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile. The results show that membrane related functions of calcium and 5HT are critical for true bystander effect expression. Our original inter-animal experiments used fish species whole body irradiated with low doses of X-rays, which prevented us from addressing the abscopal effect question. Data which are much more relevant in radiotherapy are now available for rats which received high dose local irradiation to the implanted right brain glioma. The data were generated using quasi-parallel microbeams at the biomedical beamline at the European Synchrotron Radiation Facility in Grenoble France. This means we can directly compare abscopal and "true" bystander effects in a rodent tumour model. Analysis of right brain hemisphere, left brain and urinary bladder in the directly irradiated animals and their unirradiated partners strongly suggests that bystander effects (in partner animals) are not the same as abscopal effects (in the irradiated animal). Furthermore, the presence of a tumour in the right brain alters the magnitude of both abscopal and bystander effects in the tissues from the directly irradiated animal and in the unirradiated partners which did not contain tumours, meaning the type of signal was different. PMID:25817634

  9. Anti-leukaemia activity as a bystander effect of graft-versus-host reactions.

    PubMed Central

    Johnson, P. R.; Hersey, P.

    1976-01-01

    The production of graft-versus-host (GVH) reactions in (PVGc X Wistar) F1 hybrids by the transfer of PVGc spleen cells resulted in significant resistance of these recipients to a subsequent challenge with the PVGc leukaemia. Protection was markedly dependent on dose and timing of allogeneic cell transfer and was abrogated by irradiation of the cells prior to transfer. GVH activity was shown to be a prerequisite for induction of the protective effect but was equally effective when produced by the transfer of Wistar spleen cells in place of PVGc cells. These points, plus the fact that invitro investigations of possible immune mechanisms failed to demonstrate cytotoxic immunity in treated rats, suggested a nonspecific "bystander" effect as the mechanism of protection. The implications of such a mechanism are discussed. PMID:5100

  10. Effects of a Rape Awareness Program on College Women: Increasing Bystander Efficacy and Willingness to Intervene

    ERIC Educational Resources Information Center

    Foubert, John D.; Langhinrichsen-Rohling, Jennifer; Brasfield, Hope; Hill, Brent

    2010-01-01

    An experimental study evaluated the efficacy of a sexual assault risk-reduction program on 279 college women that focused on learning characteristics of male perpetrators and teaching bystander intervention techniques. After seeing The Women's Program, participants reported significantly greater bystander efficacy and significantly greater…

  11. Modulation of modeled microgravity on radiation-induced bystander effects in Arabidopsis thaliana.

    PubMed

    Wang, Ting; Sun, Qiao; Xu, Wei; Li, Fanghua; Li, Huasheng; Lu, Jinying; Wu, Lijun; Wu, Yuejin; Liu, Min; Bian, Po

    2015-03-01

    Both space radiation and microgravity have been demonstrated to have inevitable impact on living organisms during space flights and should be considered as important factors for estimating the potential health risk for astronauts. Therefore, the question whether radiation effects could be modulated by microgravity is an important aspect in such risk evaluation. Space particles at low dose and fluence rate, directly affect only a fraction of cells in the whole organism, which implement radiation-induced bystander effects (RIBE) in cellular response to space radiation exposure. The fact that all of the RIBE experiments are carried out in a normal gravity condition bring forward the need for evidence regarding the effect of microgravity on RIBE. In the present study, a two-dimensional rotation clinostat was adopted to demonstrate RIBE in microgravity conditions, in which the RIBE was assayed using an experimental system of root-localized irradiation of Arabidopsis thaliana (A. thaliana) plants. The results showed that the modeled microgravity inhibited significantly the RIBE-mediated up-regulation of expression of the AtRAD54 and AtRAD51 genes, generation of reactive oxygen species (ROS) and transcriptional activation of multicopy P35S:GUS, but made no difference to the induction of homologous recombination by RIBE, showing divergent responses of RIBE to the microgravity conditions. The time course of interaction between the modeled microgravity and RIBE was further investigated, and the results showed that the microgravity mainly modulated the processes of the generation or translocation of the bystander signal(s) in roots. PMID:25769184

  12. Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect

    PubMed Central

    Wang, Xingmin; Yang, Yonghong; Huycke, Mark M

    2015-01-01

    Objective Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. Design Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)—an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis. Results Primary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice. Conclusions These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. PMID:24906974

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

    PubMed Central

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

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

  14. Bystander effects, genomic instability, adaptive response, and cancer risk assessment for radiation and chemical exposures

    SciTech Connect

    Preston, R. Julian . E-mail: preston.julian@epa.gov

    2005-09-01

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard, the use of biologically based dose-response models is particularly advocated. The aim is to provide an enhanced basis for describing the nature of the dose-response curve for induced tumors at low levels of exposure. Cellular responses that might influence the nature of the dose-response curve at low exposures are understandably receiving attention. These responses (bystander effects, genomic instability, and adaptive responses) have been studied most extensively for radiation exposures. The former two could result in an enhancement of the tumor response at low doses and the latter could lead to a reduced response compared to that predicted by a linear extrapolation from high dose responses. Bystander responses, whereby cells other than those directly traversed by radiation tracks are damaged, can alter the concept of target cell population per unit dose. Similarly, induced genomic instability can alter the concept of total response to an exposure. There appears to be a role for oxidative damage and cellular signaling in the etiology of these cellular responses. The adaptive response appears to be inducible at very low doses of radiation or of some chemicals and reduces the cellular response to a larger challenge dose. It is currently unclear how these cellular toxic responses might be involved in tumor formation, if indeed they are. In addition, it is not known how widespread they are as regards inducing agents. Thus, their impact on low dose cancer risk remains to be established.

  15. Personal distress and the influence of bystanders on responding to an emergency.

    PubMed

    Hortensius, Ruud; Schutter, Dennis J L G; de Gelder, Beatrice

    2016-08-01

    Spontaneous helping behavior during an emergency is influenced by the personality of the onlooker and by social situational factors such as the presence of bystanders. Here, we sought to determine the influences of sympathy, an other-oriented response, and personal distress, a self-oriented response, on the effect of bystanders during an emergency. In four experiments, we investigated whether trait levels of sympathy and personal distress predicted responses to an emergency in the presence of bystanders by using behavioral measures and single-pulse transcranial magnetic stimulation. Sympathy and personal distress were expected to be associated with faster responses to an emergency without bystanders present, but only personal distress would predict slower responses to an emergency with bystanders present. The results of a cued reaction time task showed that people who reported higher levels of personal distress and sympathy responded faster to an emergency without bystanders (Exp. 1). In contrast to our predictions, perspective taking but not personal distress was associated with slower reaction times as the number of bystanders increased during an emergency (Exp. 2). However, the decrease in motor corticospinal excitability, a direct physiological measure of action preparation, with the increase in the number of bystanders was solely predicted by personal distress (Exp. 3). Incorporating cognitive load manipulations during the observation of an emergency suggested that personal distress is linked to an effect of bystanders on reflexive responding to an emergency (Exp. 4). Taken together, these results indicate that the presence of bystanders during an emergency reduces action preparation in people with a disposition to experience personal distress. PMID:27126708

  16. Exposures involving perturbations of the EM field have non-linear effects on radiation response and can alter the expression of radiation induced bystander effects

    NASA Astrophysics Data System (ADS)

    Mothersill, Carmel; Seymour, Colin

    2012-07-01

    Our recent data suggest there is a physical component to the bystander signal induced by radiation exposure and that alternative medicine techniques such as Reiki and acupuncture or exposures to weak EM fields alter the response of cells to direct irradiation and either altered bystander signal production or altered the response of cells receiving bystander signals. Our proposed mechanism to explain these findings is that perturbation of electromagnetic (EM) fields is central to the induction of low radiation dose responses especially non-targeted bystander effects. In this presentation we review the alternative medicine data and other data sets from our laboratory which test our hypothesis that perturbation of bio-fields will modulate radiation response in the low dose region. The other data sets include exposure to MRI, shielding using lead and or Faraday cages, the use of physical barriers to bystander signal transmission and the use of membrane channel blockers. The data taken together strongly suggest that EM field perturbation can modulate low dose response and that in fact the EM field rather than the targeted deposition of ionizing energy in the DNA may be the key determinant of dose response in a cell or organism The results also lead us to suspect that at least when chemical transmission is blocked, bystander signals can be transmitted by other means. Our recent experiments suggest light signals and volatiles are not likely. We conclude that alternative medicine and other techniques involving electromagnetic perturbations can modify the response of cells to low doses of ionizing radiation and can induce bystander effects similar to those seen in medium transfer experiments. In addition to the obvious implications for mechanistic studies of low dose effects, this could perhaps provide a novel target to exploit in space radiation protection and in optimizing therapeutic gain during radiotherapy.

  17. The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104

    PubMed Central

    Foehrenbacher, Annika; Patel, Kashyap; Abbattista, Maria R.; Guise, Chris P.; Secomb, Timothy W.; Wilson, William R.; Hicks, Kevin O.

    2013-01-01

    Activation of prodrugs in tumors (e.g., by bioreduction in hypoxic zones) has the potential to generate active metabolites that can diffuse within the tumor microenvironment. Such “bystander effects” may offset spatial heterogeneity in prodrug activation but the relative importance of this effect is not understood. Here, we quantify the contribution of bystander effects to antitumor activity for the first time, by developing a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) model for PR-104, a phosphate ester pre-prodrug that is converted systemically to the hypoxia-activated prodrug PR-104A. Using Green’s function methods we calculated concentrations of oxygen, PR-104A and its active metabolites, and resultant cell killing, at each point of a mapped three-dimensional tumor microregion. Model parameters were determined in vitro, using single cell suspensions to determine relationships between PR-104A metabolism and clonogenic cell killing, and multicellular layer (MCL) cultures to measure tissue diffusion coefficients. LC-MS/MS detection of active metabolites in the extracellular medium following exposure of anoxic single cell suspensions and MCLs to PR-104A confirmed that metabolites can diffuse out of cells and through a tissue-like environment. The SR-PK/PD model estimated that bystander effects contribute 30 and 50% of PR-104 activity in SiHa and HCT116 tumors, respectively. Testing the model by modulating PR-104A-activating reductases and hypoxia in tumor xenografts showed overall clonogenic killing broadly consistent with model predictions. Overall, our data suggest that bystander effects are important in PR-104 antitumor activity, although their reach may be limited by macroregional heterogeneity in hypoxia and reductase expression in tumors. The reported computational and experimental techniques are broadly applicable to all targeted anticancer prodrugs and could be used to identify strategies for rational prodrug optimization. PMID

  18. Concise Review: The Bystander Effect: Mesenchymal Stem Cell-Mediated Lung Repair.

    PubMed

    Savukinas, Ulrika Blank; Enes, Sara Rolandsson; Sjöland, Annika Andersson; Westergren-Thorsson, Gunilla

    2016-06-01

    Mesenchymal stem or stromal cells (MSCs), a heterogeneous subset of adult stem/progenitor cells, have surfaced as potential therapeutic units with significant clinical benefit for a wide spectrum of disease conditions, including those affecting the lung. Although MSCs carry both self-renewal and multilineage differentiation abilities, current dogma holds that MSCs mainly contribute to tissue regeneration and repair by modulating the host tissue via secreted cues. Thus, the therapeutic benefit of MSCs is thought to derive from so called bystander effects. The regenerative mechanisms employed by MSCs in the lung include modulation of the immune system as well as promotion of epithelial and endothelial repair. Apart from secreted factors, a number of recent findings suggest that MSCs engage in mitochondrial transfer and shedding of membrane vesicles as a means to enhance tissue repair following injury. Furthermore, it is becoming increasingly clear that MSCs are an integral component of epithelial lung stem cell niches. As such, MSCs play an important role in coupling information from the environment to stem and progenitor populations, such that homeostasis can be ensured even in the face of injury. It is the aim of this review to outline the major mechanisms by which MSCs contribute to lung regeneration, synthesizing recent preclinical findings with data from clinical trials and potential for future therapy. Stem Cells 2016;34:1437-1444. PMID:26991735

  19. H2AX phosphorylation in response to DNA double-strand break formation during bystander signalling: effect of microRNA knockdown

    PubMed Central

    Dickey, Jennifer S.; Zemp, Franz J.; Altamirano, Alvin; Sedelnikova, Olga A.; Bonner, William M.; Kovalchuk, Olga

    2011-01-01

    Upon DNA double-strand break (DSB) formation, hundreds of H2AX molecules in the chromatin flanking the break site are phosphorylated on serine residue 139, termed gamma-H2AX, so that virtually every DSB site in a nucleus can be visualised within 10 min of its formation using an antibody to gamma-H2AX. One application of this sensitive assay is to examine the induction of DNA double-strand damage in subtle non-targeted cellular effects such as the bystander effect. Here whether microRNA (miRNA) serve as a primary signalling mechanism for bystander effect propagation by comparing matched human colon carcinoma cell lines with wild-type or depleted levels of mature miRNAs was investigated. No major differences were found in the levels of induced gamma-H2AX foci in the tested cell lines, indicating that though miRNAs play a role in bystander effect manifestation, they appear not to be the primary bystander signalling molecules in the formation of bystander effect-induced DSBs. PMID:21183548

  20. Vulnerable Children in Varying Classroom Contexts: Bystanders' Behaviors Moderate the Effects of Risk Factors on Victimization

    ERIC Educational Resources Information Center

    Karna, Antti; Voeten, Marinus; Poskiparta, Elisa; Salmivalli, Christina

    2010-01-01

    We examined whether the bystanders' behaviors in bullying situations influence vulnerable students' risk for victimization. The sample consisted of 6,980 primary school children from Grades 3-5, who were nested within 378 classrooms in 77 schools. These students filled out Internet-based questionnaires in their schools' computer labs. The results…

  1. “Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

  2. Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune

    NASA Technical Reports Server (NTRS)

    Hall, E. J.

    2001-01-01

    The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses.

  3. Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune.

    PubMed

    Hall, E J

    2001-01-01

    The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses. PMID:11770531

  4. Cytosine Deaminase/5-Fluorocytosine Exposure Induces Bystander and Radiosensitization Effects in Hypoxic Glioblastoma Cells in vitro

    SciTech Connect

    Chen, Jennifer K.; Hu, Lily J.; Wang Dongfang; Lamborn, Kathleen R.; Deen, Dennis F. . E-mail: dennisdeen@juno.com

    2007-04-01

    Purpose: Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study, we investigated whether cytosine deaminase (CD)/5-fluorocytosine (5-FC) enzyme/prodrug treatment induced a bystander effect (BE) and/or radiosensitization in hypoxic GBM cells. Methods and Materials: We stably transfected cells with a gene construct consisting of the SV40 minimal promoter, nine copies of a hypoxia-responsive element, and the yeast CD gene. During hypoxia, a hypoxia-responsive element regulates expression of the CD gene and facilitates the conversion of 5-FC to 5-fluorouracil, a highly toxic antimetabolite. We used colony-forming efficiency (CFE) and immunofluorescence assays to assess for BE in co-cultures of CD-expressing clone cells and parent, pNeo- or green fluorescent protein-stably transfected GBM cells. We also investigated the radiosensitivity of CD clone cells treated with 5-FC under hypoxic conditions, and we used flow cytometry to investigate treatment-induced cell cycle changes. Results: Both a large BE and radiosensitization occurred in GBM cells under hypoxic conditions. The magnitude of the BE depended on the number of transfected cells producing CD, the functionality of the CD, the administered concentration of 5-FC, and the sensitivity of cell type to 5-fluorouracil. Conclusion: Hypoxia-inducible CD/5-FC therapy in combination with radiation therapy shows both a pronounced BE and a radiosensitizing effect under hypoxic conditions.

  5. The Effects of Cell Phone Conversations on the Attention and Memory of Bystanders

    PubMed Central

    Galván, Veronica V.; Vessal, Rosa S.; Golley, Matthew T.

    2013-01-01

    The pervasive use of cell phones impacts many people–both cell phone users and bystanders exposed to conversations. This study examined the effects of overhearing a one-sided (cell phone) conversation versus a two-sided conversation on attention and memory. In our realistic design, participants were led to believe they were participating in a study examining the relationship between anagrams and reading comprehension. While the participant was completing an anagram task, the researcher left the room and participants overheard a scripted conversation, either two confederates talking with each other or one confederate talking on a cell phone. Upon the researcher’s return, the participant took a recognition memory task with words from the conversation, and completed a questionnaire measuring the distracting nature of the conversation. Participants who overheard the one-sided conversation rated the conversation as significantly higher in distractibility than those who overheard the two-sided conversation. Also, participants in the one-sided condition scored higher on the recognition task. In particular they were more confident and accurate in their responses to words from the conversation than participants in the two-sided condition. However, participants’ scores on the anagram task were not significantly different between conditions. As in real world situations, individual participants could pay varying amounts of attention to the conversation since they were not explicitly instructed to ignore it. Even though the conversation was irrelevant to the anagram task and contained less words and noise, one-sided conversations still impacted participants’ self-reported distractibility and memory, thus showing people are more attentive to cell phone conversations than two-sided conversations. Cell phone conversations may be a common source of distraction causing negative consequences in workplace environments and other public places. PMID:23516514

  6. Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish.

    PubMed

    Smith, Richard W; Seymour, Colin B; Moccia, Richard D; Mothersill, Carmel E

    2016-02-01

    The bystander effect, a non-targeted effect (NTE) of radiation, which describes the response by non-irradiated organisms to signals emitted by irradiated organisms, has been documented in a number of fish species. However transgenerational effects of radiation (including NTE) have yet to be studied in fish. Therefore rainbow trout, which were irradiated as eggs at 48h after fertilisation, eyed eggs, yolk sac larvae or first feeders, were bred to generate a F1 generation and these F1 fish were bred to generate a F2 generation. F1 and F2 fish were swam with non-irradiated bystander fish. Media from explants of F1 eyed eggs, F1 one year old fish gill and F1 two year old fish gill and spleen samples, and F2 two year old gill and spleen samples, as well as from bystander eggs/fish, was used to treat a reporter cell line, which was then assayed for changes in cellular survival/growth. The results were complex and dependent on irradiation history, age (in the case of the F1 generation), and were tissue specific. For example, irradiation of one parent often resulted in effects not seen with irradiation of both parents. This suggests that, unlike mammals, in certain circumstances maternal and paternal irradiation may be equally important. This study also showed that trout can induce a bystander effect 2 generations after irradiation, which further emphasises the importance of the bystander effect in aquatic radiobiology. Given the complex community structure in aquatic ecosystems, these results may have significant implications for environmental radiological protection. PMID:26618503

  7. The effect of victims' responses to overt bullying on same-sex peer bystander reactions.

    PubMed

    Sokol, Nicole; Bussey, Kay; Rapee, Ronald M

    2015-10-01

    This study investigated the impact of victims' responses to overt bullying on peer bystanders' attitudes and reactions. Fifth- and seventh-grade students (N = 206; M(age) = 11.13 and 13.18 years, respectively) completed online questionnaires about gender-consistent videotaped hypothetical bullying scenarios in which the victims' responses (angry, sad, confident, ignoring) were experimentally manipulated. Victims' responses significantly influenced bystanders' attitudes towards the victim, perceptions of the victimization, emotional reactions, and behavioral intentions. In general, angry victims elicited more negative reactions, sad victims elicited greater intentions to act, while incidents involving confident victims were perceived as less serious. Several variations depending on the bullying type and students' grade, gender, and personal experiences with bullying were evident. Implications for individual-level and peer-level anti-bullying interventions are discussed. PMID:26407835

  8. The impact of onlooking and including bystander behaviour on judgments and emotions regarding peer exclusion.

    PubMed

    Malti, Tina; Strohmeier, Dagmar; Killen, Melanie

    2015-09-01

    We investigated judgments and emotions in contexts of social exclusion that varied as a function of bystander behaviour (N = 173, 12- and 16-year-olds). Adolescents responded to film vignettes depicting a target excluded by a group with no bystanders, onlooking bystanders, or bystanders who included the target. Adolescents were asked to judge the behaviour and attribute emotions to the excluding group, the excluded target, and the bystanders. Younger adolescents judged the behaviour of the excluding group as more wrong than older adolescents when there were no bystanders present, indicating that the presence of bystanders was viewed as lessening the negative outcome of exclusion by the younger group. Yet, bystanders play a positive role only when they are includers, not when they are silent observers. This distinction was revealed by the findings that adolescents rated the behaviour of onlooking bystanders as more wrong compared with the behaviour of including bystanders. Moreover, all adolescents justified the inclusive behaviour more frequently with empathy than the onlooking behaviour. Adolescents also anticipated more empathy to including bystanders than to onlooking bystanders, as well as anticipated more guilt to onlooking bystanders than including bystanders. The findings are discussed in light of the role of group norms and group processes regarding bystanders' roles in social exclusion peer encounters. PMID:25953459

  9. Virtual bystanders in a language lesson: examining the effect of social evaluation, vicarious experience, cognitive consistency and praising on students' beliefs, self-efficacy and anxiety in a virtual reality environment.

    PubMed

    Qu, Chao; Ling, Yun; Heynderickx, Ingrid; Brinkman, Willem-Paul

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people's beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants' heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders' positive attitude towards peer students, participants' self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders' attitudes towards virtual peers and the participants was not found to result in a larger change in the participants' beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants' beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people's beliefs, anxiety and behavior. PMID:25884211

  10. Bystander effects of PC12 cells treated with Pb²⁺ depend on ROS-mitochondria-dependent apoptotic signaling via gap-junctional intercellular communication.

    PubMed

    Guo, Shu; Zhou, Jin; Chen, Xuemei; Yu, Yunjiang; Ren, Mingzhong; Hu, Guocheng; Liu, Yun; Zou, Fei

    2014-08-17

    The demonstration of bystander effect, which means injured cells propagate damage to neighboring cells, in whole organisms has clear implication of the potential relevance of the non-targeted response to human health. Here we show that 10 μM lead acetate, the optimum concentration for inducing apoptosis confirmed by the expression levels of Bax and Bcl-2, can also induce rat pheochromocytoma (PC12) cells to exert bystander effects to neighboring cells. In a novel co-culture system, GFP-PC12 (Pb(2+)) cells, which were stable transfected with EF1A-eGFP and pre-exposed with lead acetate, were co-cultured with unexposed PC12 cells at a 1:5 ratio. Parachute assays demonstrated the functional gap-junctional intercellular communication (GJIC) formed between Pb(2+)-exposed and unexposed cells. The Pb(2+)-exposed cells induced very similar effects on neighboring unexposed cells to apoptosis coincide with intracellular ROS generation and the collapse of mitochondrial membrane potential (Δψm). Furthermore, carbenoxolone (CBX), a blocker of GJIC, inhibited the bystander effects. The results indicate that the Pb(2+)-induced insults propagate through GJIC between PC12 cells, while inducing the bystander cells to apoptosis via ROS-mitochondria-dependent apoptotic signaling. PMID:24960054

  11. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation.

    PubMed

    Xie, Yuexia; Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen; Shao, Chunlin

    2015-02-01

    Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved. PMID:25772107

  12. Novel mechanism for the radiation-induced bystander effect: nitric oxide and ethylene determine the response in sponge cells.

    PubMed

    Müller, Werner E G; Ushijima, Hiroshi; Batel, Renato; Krasko, Anatoli; Borejko, Alexandra; Müller, Isabel M; Schröder, Heinz-C

    2006-05-11

    Until now the bystander effect had only been described in vertebrates. In the present study the existence of this effect has been demonstrated for the phylogenetically oldest metazoan phylum, the Porifera. We used the demosponge Suberites domuncula for the experiments in the two-chamber-system. The lower dish contained irradiated "donor" cells (single cells) and the upper dish the primmorphs ("recipient" primmorphs). The "donor" cells were treated with UV-B light (40 mJ/cm2) and 100 microM hydrogen peroxide (H2O2), factors that exist also in the natural marine aquatic environment of sponges; these factors caused a high level of DNA strand breaks followed by a reduced viability of the cells. If these cells were added to the "recipient" primmorphs these 3D-cell cultures started to undergo apoptosis. This effect could be abolished by the NO-specific scavenger PTIO and ethylene. The conclusion that NO is synthesized by the UV-B/H2O2-treated cells was supported analytically. The cDNA encoding the enzyme dimethylarginine dimethylaminohydrolase (DDAH) was isolated from the "donor" cells. High levels of DDAH transcripts were measured in UV-B/H2O2-treated "donor" cells while after ethylene treatment the steady-state level of expression drops drastically. We conclude that in the absence of ethylene the concentration of the physiological inhibitor for the NO synthase ADMA is low, due to the high level of DDAH. In consequence, high amounts of NO are released from "donor" cells which cause apoptosis in "recipient" primmorphs. In contrast, ethylene reduces the DDAH expression with the consequence of higher levels of ADMA which prevent the formation of larger amounts of NO. This study describes the radiation-induced bystander effect also for the most basal metazoans and demonstrates that this effect is controlled by the two gases NO and ethylene. PMID:16427660

  13. Irradiated fibroblast-induced bystander effects on invasive growth of squamous cell carcinoma under cancer-stromal cell interaction.

    PubMed

    Kamochi, Noriyuki; Nakashima, Masahiro; Aoki, Shigehisa; Uchihashi, Kazuyoshi; Sugihara, Hajime; Toda, Shuji; Kudo, Sho

    2008-12-01

    The irradiated fibroblast-induced response of non-irradiated neighboring cells is called 'radiation-induced bystander effect', but it is unclear in non-irradiated human squamous cell carcinoma (SCC) cells. The present study shows that irradiated fibroblasts promoted the invasive growth of T3M-1 SCC cells, but not their apoptosis, more greatly than non-irradiated fibroblasts, using collagen gel invasion assay, immunohistochemistry and Western blot. The number of irradiated fibroblasts decreased to about 30% of that of non-irradiated fibroblasts, but irradiated fibroblasts increased the growth marker ki-67 display of SCC cells more greatly than non-irradiated fibroblasts. Irradiated fibroblasts did not affect the apoptosis marker ss-DNA expression of SCC cells. Irradiated fibroblasts enhanced the display of the following growth-, invasion- and motility-related molecules in SCC cells more greatly than non-irradiated fibroblasts: c-Met, Ras, mitogen-activated protein kinase (MAPK) cascade (Raf-1, MEK-1 and ERK-1/2), matrix metalloproteinase-1 and -9, laminin 5 and filamin A. Irradiated fibroblasts, but not non-irradiated ones, formed irradiation-induced foci (IRIF) of the genomic instability marker p53-binding protein 1 (53BP1) and expressed transforming growth factor-beta1 (TGF- beta1). Irradiated fibroblasts in turn enabled SCC cells to enhance 53BP1 IRIF formation more extensively than non-irradiated fibroblasts. Finally, effects of irradiated fibroblasts on growth and apoptosis of another HEp-2 SCC cell type were similar to those of T3M-1. These results suggest that irradiated fibroblasts promotes invasion and growth of SCC cells by enhancement of invasive growth-related molecules above through TGF- beta1-mediated bystander mechanism, in which irradiated fibroblast-induced genomic instability of SCC cells may be involved. PMID:19018771

  14. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells

    SciTech Connect

    Marianne B. Sowa; Wilfried Goetz; Janet E. Baulch; Dinah N. Pyles; Jaroslaw Dziegielewski; Susannah Yovino; Andrew R. Snyder; Sonia M. de Toledo; Edouard I. Azzam; William F. Morgan

    2008-06-30

    Purpose: To investigate radiation induced bystander responses and to determine the role of gap junction intercellular communication and the radiation environment in propagating this response. Materials and Methods: We use medium transfer and targeted irradiation to examine radiation induced bystander effects in primary human fibroblast (AG1522) and human colon carcinoma (RKO36) cells. We examined the effect of variables such as gap junction intercellular communication, linear energy transfer (LET), and the role of the radiation environment in non-targeted responses. Endpoints included clonogenic survival, micronucleus formation and foci formation at histone 2AX over doses ranging from 10 to 100 cGy. Results: The results show no evidence of a low-LET radiation induced bystander response for the endpoints of clonogenic survival and induction of DNA damage. Nor do we see evidence of a high-LET, Fe ion radiation (1 GeV/n) induced bystander effect. However, direct comparison for 3.2 MeV α-particle exposures showed a statistically significant medium transfer bystander effect for this high-LET radiation. Conclusions: From our results, it is evident that there are many confounding factors influencing bystander responses as reported in the literature. Our observations reflect the inherent variability in biological systems and the difficulties in extrapolating from in vitro models to radiation risks in humans.

  15. The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.

    PubMed

    Hanu, C; Timotin, E; Wong, R; Sur, R K; Hayward, J E; Seymour, C B; Mothersill, C E

    2016-05-01

    The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy. PMID:26750714

  16. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  17. Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

    SciTech Connect

    Balderson, M.J.; Kirkby, C.

    2014-08-15

    In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.

  18. Virtual Bystanders in a Language Lesson: Examining the Effect of Social Evaluation, Vicarious Experience, Cognitive Consistency and Praising on Students' Beliefs, Self-Efficacy and Anxiety in a Virtual Reality Environment

    PubMed Central

    Qu, Chao; Ling, Yun; Heynderickx, Ingrid; Brinkman, Willem-Paul

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people’s beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants’ heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders’ positive attitude towards peer students, participants’ self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders’ attitudes towards virtual peers and the participants was not found to result in a larger change in the participants’ beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants’ beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people’s beliefs, anxiety and behavior. PMID:25884211

  19. Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

    PubMed Central

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2012-01-01

    Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

  20. G(2)-M phase-correlative bystander effects are co-mediated by DNA-PKcs and ATM after carbon ion irradiation.

    PubMed

    Tu, Wenzhi; Dong, Chen; Konishi, Teruaki; Kobayashi, Alisa; Furusawa, Yoshiya; Uchihori, Yukio; Xie, Yuexia; Dang, Bingrong; Li, Wenjian; Shao, Chunlin

    2016-01-01

    Accumulated evidence has shown that radiation-induced bystander effect (RIBE) may have significant implications to the efficiency of radiotherapy. Although cellular radiosensitivity relies on cell cycle status, it is largely unknown how about the relationship between RIBE and cell cycle distribution, much less the underlying mechanism. In the present study, the lung cancer A549 cells were synchronized into different cell cycle phases of G1, S and G2/M and irradiated with high linear energy transfer (LET) carbon ions. By treating nonirradiated cells with the conditioned medium from these irradiated cells, it was found that the G2-M phase cells had the largest contribution to RIBE. Meanwhile, the activity of DNA-PKcs but not ATM was increased in the synchronized G2-M phase cells in spite of both of them were activated in the asynchronous cells after carbon ion irradiation. When the G2-M phased cells were transferred with DNA-PKcs siRNA and ATM siRNA individually or treated with an inhibitor of either DNA-PKcs or ATM before carbon ion irradiation, the RIBE was effectively diminished. These results provide new evidence linking cell cycle to bystander responses and demonstrate that DNA-PKcs and ATM are two associated factors in co-regulating G2-M phase-related bystander effects. PMID:26774662

  1. Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.

    PubMed

    Fernandez-Palomo, Cristian; Schültke, Elisabeth; Bräuer-Krisch, Elke; Laissue, Jean Albert; Blattmann, Hans; Seymour, Colin; Mothersill, Carmel

    2016-08-01

    Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor-bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved. PMID:27356059

  2. A Variable-Energy Soft X-Ray Microprobe to Investigate Mechanisms of the Radiation-Induced Bystander Effect.

    SciTech Connect

    Folkard, Melvyn; Vojnovic, Borivoj; Schettino, Giuseppe; Atkinson, Kirk; Prise, Kevin, M.; Michael, Barry, D.

    2007-01-23

    The Gray Cancer Institute has pioneered the use of X ray focussing techniques to develop systems for micro irradiating individual cells and sub cellular targets in vitro. Cellular micro irradiation is now recognised as a highly versatile technique for understanding how ionising radiation interacts with living cells and tissues. The strength of the technique lies in its ability to deliver precise doses of radiation to selected individual cells (or sub cellular targets). The application of this technique in the field of radiation biology continues to be of great interest for investigating a number of phenomena currently of concern to the radiobiological community. One important phenomenon is the so called ‘bystander effect’ where it is observed that unirradiated cells can also respond to signals transmitted by irradiated neighbours. Clearly, the ability of a microbeam to irradiate just a single cell or selected cells within a population is well suited to studying this effect. Our prototype ‘tabletop’ X-ray microprobe was optimised for focusing 278 eV C-K X rays and has been used successfully for a number of years. However, we have sought to develop a new variable energy soft X-ray microprobe capable of delivering focused CK (0.28 keV), Al-K (1.48 keV) and notably, Ti-K (4.5 keV) X rays. Ti-K X rays are capable of penetrating several cell layers and are therefore much better suited to studies involving tissues and multi cellular layers. In our new design, X-rays are generated by the focussed electron bombardment of a material whose characteristic-K radiation is required. The source is mounted on a 1.5 x 1.0 metre optical table. Electrons are generated by a custom built gun, designed to operate up to 15 kV. The electrons are focused using a permanent neodymium iron boron magnet assembly. Focusing is achieved by adjusting the accelerating voltage and by fine tuning the target position via a vacuum position feedthrough. To analyze the electron beam properties, a

  3. Evaluation of Bystander Cell Killing Effects in Suicide Gene Therapy of Cancer: Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis.

    PubMed

    Sato, Takeya; Neschadim, Anton; Nakagawa, Ryo; Yanagisawa, Teruyuki; Medin, Jeffrey A

    2015-01-01

    Suicide gene therapy of cancer (SGTC) entails the introduction of a cDNA sequence into tumor cells whose polypeptide product is capable of either directly activating apoptotic pathways itself or facilitating the activation of pharmacologic agents that do so. The latter class of SGTC approaches is of the greater utility in cancer therapy owing to the ability of some small, activated cytotoxic compounds to diffuse from their site of activation into neighboring malignant cells, where they can also mediate destruction. This phenomenon, termed "bystander killing", can be highly advantageous in driving significant tumor regression in vivo without the requirement of transduction of each and every tumor cell with the suicide gene. We have developed a robust suicide gene therapy enzyme/prodrug system based on an engineered variant of the human thymidylate kinase (TMPK), which has been endowed with the ability to drive azidothymidine (AZT) activation. Delivery of this suicide gene sequence into tumors by means of recombinant lentivirus-mediated transduction embodies an SGTC strategy that successfully employs bystander cell killing as a mechanism to achieve significant ablation of solid tumors in vivo. Thus, this engineered TMPK/AZT suicide gene therapy axis holds great promise for clinical application in the treatment of inoperable solid tumors in the neoadjuvant setting. Here we present detailed procedures for the preparation of recombinant TMPK-based lentivirus, transduction of target cells, and various approaches for the evaluation of bystander cell killing effects in SGCT in both in vitro and in vivo models. PMID:26072401

  4. Evaluation of a bystander education program.

    PubMed

    Amar, Angela Frederick; Sutherland, Melissa; Kesler, Erin

    2012-12-01

    Sexual and partner violence are widespread problems on college campuses. By changing attitudes, beliefs, and behavior, bystander education programs have been found to prevent sexual and partner violence and improve the responses of peers to survivors. The purpose of this study is to evaluate the effectiveness and feasibility of a bystander education program that was adapted to a specific university setting. A convenience sample of 202, full-time undergraduate students aged 18-22 years participated in the bystander education program and completed pre- and post-test measures of attitudes related to sexual and partner violence and willingness to help. Paired sample t-tests were used to examine changes in scores between pre- and post-test conditions. After the program, participants' reported decreased rape myth acceptance and denial of interpersonal violence, and increased intention to act as a bystander and an increased sense of responsibility to intervene. Mental health nurses can use principles of bystander education in violence prevention programs and in providing support to survivors. PMID:23215986

  5. Alternative Medicine Techniques Have Non-Linear Effects on Radiation Response and Can Alter the Expression of Radiation Induced Bystander Effects

    PubMed Central

    Mothersill, Carmel; Smith, Richard; Henry, Matthew; Seymour, Colin; Wong, Raimond

    2013-01-01

    Many so-called “alternative medicine” techniques such as Reiki and acupuncture produce very good outcomes for intractable pain and other chronic illnesses but the efficacy is often dismissed as being psychosomatic. However a plausible mechanism does exist i.e. that the treatments alter the electromagnetic fields in living organisms and thereby prevent or reduce activity of neurons which lead to the pain. Low doses of ionising radiation have similar effects on electromagnetic fields and are known to induce signaling cascades in tissues due to ion gradients. To test this hypothesis cell cultures were exposed to Reiki – like and to acupuncture – like treatments, both performed by qualified practitioners. The cells were exposed either before or after the treatment to x-rays and were monitored for production of direct damage or bystander signals. The data suggest that the alternative techniques altered the response of cells to direct irradiation and altered bystander signal mechanisms. We conclude that alternative medicine techniques involving electromagnetic perturbations may modify the response of cells to ionizing radiation. In addition to the obvious implications for mechanistic studies of low dose effects, this could provide a novel target to exploit in radiation protection and in optimizing therapeutic gain during radiotherapy. PMID:23550268

  6. Sex differences in bystander intervention in a theft.

    PubMed

    Austin, W

    1979-11-01

    A series of studies demonstrated a strong relationship among the situation-defining variable of degree of harm to victim, sexual configuration among participants, and bystanders' willingness to intervene to stop a theft. A pretest showed that a prior verbal commitment was absolutely necessary for intervention. The remaining data showed that high harm to a victim produced a high rate of intervention and showed strong sex differences in helping behavior in low-harm conditions. A high percentage of female bystanders helped in both low- and high-harm situations, whereas frequent helping by males was observed only when harm to the victim was high. Female victims elicited a significantly greater amount of helping, and sex of thief had no effect. A significant sex of bystander, sex of victim, and harm to victim interaction best describes the data. Results are interpreted in terms of different motivational sets held by males and females when they are responsible for the fate of others. Results also support the utility of an interactionist approach to the question of how individual and situational variables influence prosocial action. PMID:521904

  7. A Mouse Ear Model for Bystander Studies Induced by Microbeam Irradiation

    PubMed Central

    Buonanno, M.; Randers-Pehrson, G.; Smilenov, L. B.; Kleiman, N. J.; Young, E.; Ponnayia, B.; Brenner, D. J.

    2015-01-01

    Radiation-induced bystander effects have been observed in vitro and in cell and tissue culture models, however, there are few reported studies showing these effects in vivo. To our knowledge, this is the first reported study on bystander effects induced by microbeam irradiation in an intact living mammal. The mouse ear was used to investigate radiation-induced bystander effects in keratinocytes, utilizing a 3 MeV proton microbeam (LET 13.1 keV/µm) with a range in skin of about 135 µm. Using a custom-designed holder, the ear of an anesthetized C57BL/6J mouse was flattened by gentle suction and placed over the microbeam port to irradiate cells along a 35 µm wide, 6 mm long path. Immunohistochemical analysis of γ-H2AX foci formation in tissue sections revealed, compared to control tissue, proton-induced γ-H2AX foci formation in one of the two epidermal layers of the mouse ear. Strikingly, a higher number of cells than expected showed foci from direct irradiation effects. Although the proton-irradiated line was ~35 µm wide, the average width spanned by γ-H2AX-positive cells exceeded 150 µm. Cells adjacent to or in the epidermal layer opposite the γ-H2AX-positive region did not exhibit foci. These findings validate this mammalian model as a viable system for investigating radiation-induced bystander effects in an intact living organism. PMID:26207682

  8. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions.

    PubMed

    Buonanno, Manuela; De Toledo, Sonia M; Howell, Roger W; Azzam, Edouard I

    2015-05-01

    During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low 'flux' of the high atomic number and high energy (HZE) radiations relative to the higher 'flux' of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel. PMID:25805407

  9. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions

    PubMed Central

    Buonanno, Manuela; De Toledo, Sonia M.; Howell, Roger W.; Azzam, Edouard I.

    2015-01-01

    During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low ‘flux’ of the high atomic number and high energy (HZE) radiations relative to the higher ‘flux’ of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel. PMID:25805407

  10. Predicting Improvement After a Bystander Program for the Prevention of Sexual and Dating Violence.

    PubMed

    Hines, Denise A; Palm Reed, Kathleen M

    2015-07-01

    Although evidence suggests that bystander prevention programs are promising interventions for decreasing sexual violence and dating violence on college campuses, there have been no studies to date evaluating moderators of bystander program effectiveness. The current study evaluates whether different demographic characteristics, attitudes, knowledge, and behaviors at pretest predict change over a 6-month follow-up for students who participated in a bystander prevention program. Participants in the three assessments (pretest, posttest, 6-month follow-up) included 296 college students who were mandated to attend a bystander program during their first year orientation. Analyses showed that with few exceptions, the bystander program worked best for students who were most at risk given their pretest demographics and levels of attitudes condoning dating violence and sexual violence, bystander efficacy, and bystander behaviors. Results are discussed in terms of suggestions for future research. PMID:25380846

  11. Activation of caspase-3 noninvolved in the bystander effect of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system.

    PubMed

    Zhang, Zhihong; Lin, Juqiang; Chu, Jun; Ma, Yan; Zeng, Shaoqun; Luo, Qingming

    2008-01-01

    Use of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system is one of the promising approaches in the rapidly growing area of gene therapy. The "bystander effect," a phenomenon in which HSV-tk+ cells exposed to GCV are toxic to adjacent HSV-tk- cells, was reported to play an important role in suicide gene therapy. However, the mechanism by which HSV-tk/GCV induces the bystander effect is poorly understood. We monitored the activation of caspase-3 in living cells induced by the HSV-tk/GCV system using a genetically encoded fluorescence resonance energy transfer (FRET) probe CD3, , a caspase-3 recognition site fused with a cyan fluorescent protien (CFP) and a red fluorescent protein (DsRed) which we reported and named in a previous paper. Fluorescence protein (FP)-based multicolor cellular labeling, combined with the multichannel fluorescence imaging and FRET imaging techniques, provides a novel and improved approach to directly determine whether the activation of caspase-3 involved in the HSV-tk/GCV system induces cell apoptosis in tk gene-expressing cells and their neighboring cells. FRET ratio images of CD3, and fluorescence images of the fusion protein of thymidine kinase linked with green fluorescent protein (TK-GFP), indicated that HSV-tk/GCV system-induced apoptosis in human adenoid cystic carcinoma (ACC-M) cells was via a caspase-3 pathway, and the activation of caspase-3 was not involved in the bystander effect of HSV-tk/GCV system. PMID:18601533

  12. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    SciTech Connect

    Gordon, J; Snyder, K; Zhong, H; Chetty, I

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  13. Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress.

    PubMed

    Buonanno, Manuela; de Toledo, Sonia M; Pain, Debkumar; Azzam, Edouard I

    2011-04-01

    Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ∼ 151 keV/µm), 600 MeV/u silicon ions (LET ∼ 51 keV/µm), or 1 GeV protons (LET ∼ 0.2 keV/µm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-µm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy. PMID:21319986

  14. Long-Term Consequences of Radiation-Induced Bystander Effects Depend on Radiation Quality and Dose and Correlate with Oxidative Stress

    PubMed Central

    Buonanno, Manuela; de Toledo, Sonia M.; Pain, Debkumar; Azzam, Edouard I.

    2011-01-01

    Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ~ 151 keV/μm), 600 MeV/u silicon ions (LET ~ 51 keV/μm), or 1 GeV protons (LET ~ 0.2 keV/μm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-μm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy. PMID:21319986

  15. Evaluation of Green Dot: an active bystander intervention to reduce sexual violence on college campuses.

    PubMed

    Coker, Ann L; Cook-Craig, Patricia G; Williams, Corrine M; Fisher, Bonnie S; Clear, Emily R; Garcia, Lisandra S; Hegge, Lea M

    2011-06-01

    Using a cross-sectional survey of a random sample of 7,945 college undergraduates, we report on the association between having received Green Dot active bystander behavior training and the frequency of actual and observed self-reported active bystander behaviors as well as violence acceptance norms. Of 2,504 students aged 18 to 26 who completed the survey, 46% had heard a Green Dot speech on campus, and 14% had received active bystander training during the past 2 years. Trained students had significantly lower rape myth acceptance scores than did students with no training. Trained students also reported engaging in significantly more bystander behaviors and observing more self-reported active bystander behaviors when compared with nontrained students. When comparing self-reported active bystander behavior scores of students trained with students hearing a Green Dot speech alone, the training was associated with significantly higher active bystander behavior scores. Those receiving bystander training appeared to report more active bystander behaviors than those simply hearing a Green Dot speech, and both intervention groups reported more observed and active bystander behaviors than nonexposed students. PMID:21642269

  16. Student Voices: What Can Bystanders Do to Prevent Bullying of Students Who Are Different (or Perceived as Different) from Others?

    ERIC Educational Resources Information Center

    Nordseth, Anna; Vepachedu, Vikas; Shipman, Grant; Alayachew, David

    2012-01-01

    In this article, four students share their ideas on what bystanders can do to prevent bullying of students who are different or perceived as different from others. Anna Nordseth says what bystanders need to realize is how to recognize bullying and what a lasting effect it can have on the individuals involved. One bold, compassionate bystander can…

  17. New Directions for Gifted Black Males Suffering from Bystander Effects: A Call for Upstanders

    ERIC Educational Resources Information Center

    Grantham, Tarek C.

    2011-01-01

    An educational crisis in Black male representation in gifted programs exists, requiring a new lens through which to view problems and find solutions. Though many people observe that Black males face extraordinary barriers to successful participation in gifted programs, many stand by, watching as they are overlooked for or drop out of gifted…

  18. Peer bystanders to bullying: who wants to play with the victim?

    PubMed

    Howard, Anne M; Landau, Steven; Pryor, John B

    2014-02-01

    Given widespread concern associated with school-based bullying, researchers have looked beyond a dyadic perspective (i.e., bullies and victims only), and now consider the broader social ecology of the peer group. In this research, we examined how the behaviors of peer bystanders influence subsequent reactions to bullies and their victims. Two hundred and six 10- to 15-year-old boys (Mage = 12.46) were invited to play a computer game with three other boys allegedly located at another school. Before the start of the game, participants "met the other players" apparently sitting in a waiting room. These child actors depicted an escalating bullying episode in which the behavior of the bystander was manipulated: aide to the bully, defender of the victim, or passive outsider. Immediately after exposure to the bullying, each participant played a ball toss game (Cyberball) with the three other boys in the video. Individual differences among participants were examined as moderators of the effect of bystander behavior on participants' willingness to include the "victim" in the game. Results indicated that, when exposed to a passive bystander, boys' normative beliefs about aggression, as well as their tendency to morally disengage from observed egregious acts, decreased their willingness to include the victim in the game. PMID:23801432

  19. Self-Protective Function of Post-Conflict Bystander Affiliation in Mandrills

    PubMed Central

    Schino, Gabriele; Marini, Claudia

    2012-01-01

    Background Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders) have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. Methodology/Principal Findings We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx). We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim's distress (as measured by its scratching rates) and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. Conclusions/Significance These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses. PMID:22715420

  20. Radiation quality dependence of signal transmission and bystander induced cell killing

    NASA Astrophysics Data System (ADS)

    Esposito, Giuseppe; Bertolotti, Alessia; Facoetti, Angelica; Grande, Sveva; Mariotti, Luca; Ottolenghi, Andrea; Ranza, Elena; Simone, Giustina; Sorrentino, Eugenio; Antonella Tabocchini, Maria

    Low dose radiobiological studies have shown effects, observable in cells that are in the vicinity of irradiated cells, which are due to the release by irradiated cells of several cellular mediators among which Reactive Oxygen and Nitrogen Species (ROS, NRS), and cytokines are likely to play a key role. Despite the large number in the literature of studies on bystander effects induced by ionizing radiation the results are still conflicting, and further studies are therefore needed on the possible underlying mechanisms. The dependence on radiation quality deserve particular attention because bystander mechanisms are probably more important with high-LET irradi-ations, where many cells are not hit (bystander). Moreover, due to the different patterns of energy deposition, the cellular response to low LET and high LET radiation can be different. Understanding whether these cells can contribute to the adverse effects of low radiation doses in a radiation quality-dependent fashion might have important implications in risk estimates for both cancer induction and non-cancer diseases. In this context, we addressed to the study of the bystander induced cell killing after incubation with "conditioned medium" from primary human fibroblasts irradiated with 0.1 and 0.5 Gy of α-particles or γ-rays. Medium transfer was performed after 1h incubation from irradiation. The results have confirmed a reduction in clonogenic survival after incubation with medium from α-irradiated cells, independently of the dose; similar results were obtained after γ-irradiation, although in this case a slight dose depen-dence could be envisaged. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were measured in the conditioned medium collected up to 20 hours after irradiation with α-particles and γ-rays in the dose-range of 0.1-1.0 Gy, in parallel with evaluation of their receptor expression in irradi-ated and bystander cells. Concerning IL-6, we observed the strongest modulation of its release

  1. Site Specific Microbeam Irradiation: Defining a Bystander Effect. Final Technical Report

    SciTech Connect

    Brenner, David J.

    2003-10-22

    There is evidence that low-energy x-rays as used in mammography have an increased biological effectiveness relative to higher-energy photons. However, the RBE values are not large, probably less than 2. Thus it is unlikely that the radiation risk alone could prove to be a ''show stopper'' regarding screening mammography because, for older women, the benefit is likely to considerably outweigh the radiation risk. Nevertheless, the RBE for low-energy x-rays might reasonably be taken into account when assessing the recommended age to commence such annual screening.

  2. Bystanders Are the Key to Stopping Bullying

    ERIC Educational Resources Information Center

    Padgett, Sharon; Notar, Charles E.

    2013-01-01

    Bullying is the dominance over another. Bullying occurs when there is an audience. Peer bystanders provide an audience 85% of instances of bullying. If you remove the audience bullying should stop. The article is a review of literature (2002-2013) on the role of bystanders; importance of bystanders; why bystanders behave as they do; resources to…

  3. The Effect of Cognitive Behavioral Therapy and Cognitive Behavioral Therapy Plus Media on the Reduction of Bullying and Victimization and the Increase of Empathy and Bystander Response in a Bully Prevention Program for Urban Sixth-Grade Students

    ERIC Educational Resources Information Center

    McLaughlin, Laura Pierce

    2009-01-01

    The purpose of this study was to investigate the effect of cognitive behavioral therapy and cognitive behavioral therapy plus media on the reduction of bullying and victimization and the increase in empathy and bystander response in a bully prevention program for urban sixth-graders. Sixty-eight students participated. Because one of the…

  4. Genomic Instability in Liver Cells Caused by an LPS-Induced Bystander-Like Effect

    PubMed Central

    Kovalchuk, Igor; Walz, Paul; Thomas, James; Kovalchuk, Olga

    2013-01-01

    Bacterial infection has been linked to carcinogenesis, however, there is lack of knowledge of molecular mechanisms that associate infection with the development of cancer. We analyzed possible effects of the consumption of heat-killed E. coli O157:H7 cells or its cellular components, DNA, RNA, protein or lipopolysaccharides (LPS) on gene expression in naïve liver cells. Four week old mice were provided water supplemented with whole heat-killed bacteria or bacterial components for a two week period. One group of animals was sacrificed immediately, whereas another group was allowed to consume uncontaminated tap water for an additional two weeks, and liver samples were collected, post mortem. Liver cells responded to exposure of whole heat-killed bacteria and LPS with alteration in γH2AX levels and levels of proteins involved in proliferation, DNA methylation (MeCP2, DNMT1, DNMT3A and 3B) or DNA repair (APE1 and KU70) as well as with changes in the expression of genes involved in stress response, cell cycle control and bile acid biosynthesis. Other bacterial components analysed in this study did not lead to any significant changes in the tested molecular parameters. This study suggests that lipopolysaccharides are a major component of Gram-negative bacteria that induce molecular changes within naïve cells of the host. PMID:23874414

  5. Systemic mechanisms and effects of ionizing radiation: A new 'old' paradigm of how the bystanders and distant can become the players.

    PubMed

    Nikitaki, Zacharenia; Mavragani, Ifigeneia V; Laskaratou, Danae A; Gika, Violeta; Moskvin, Vadim P; Theofilatos, Konstantinos; Vougas, Konstantinos; Stewart, Robert D; Georgakilas, Alexandros G

    2016-06-01

    Exposure of cells to any form of ionizing radiation (IR) is expected to induce a variety of DNA lesions, including double strand breaks (DSBs), single strand breaks (SSBs) and oxidized bases, as well as loss of bases, i.e., abasic sites. The damaging potential of IR is primarily related to the generation of electrons, which through their interaction with water produce free radicals. In their turn, free radicals attack DNA, proteins and lipids. Damage is induced also through direct deposition of energy. These types of IR interactions with biological materials are collectively called 'targeted effects', since they refer only to the irradiated cells. Earlier and sometimes 'anecdotal' findings were pointing to the possibility of IR actions unrelated to the irradiated cells or area, i.e., a type of systemic response with unknown mechanistic basis. Over the last years, significant experimental evidence has accumulated, showing a variety of radiation effects for 'out-of-field' areas (non-targeted effects-NTE). The NTE involve the release of chemical and biological mediators from the 'in-field' area and thus the communication of the radiation insult via the so called 'danger' signals. The NTE can be separated in two major groups: bystander and distant (systemic). In this review, we have collected a detailed list of proteins implicated in either bystander or systemic effects, including the clinically relevant abscopal phenomenon, using improved text-mining and bioinformatics tools from the literature. We have identified which of these genes belong to the DNA damage response and repair pathway (DDR/R) and made protein-protein interaction (PPi) networks. Our analysis supports that the apoptosis, TLR-like and NOD-like receptor signaling pathways are the main pathways participating in NTE. Based on this analysis, we formulate a biophysical hypothesis for the regulation of NTE, based on DNA damage and apoptosis gradients between the irradiation point and various distances

  6. A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

  7. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Pyles, Dinah N.; Dziegielewski, J.; Yovino, Susannah; Snyder, Andrew R.; de Toledo, S. M.; Azzam, Edouard I.; Morgan, William F.

    2010-02-01

    The conventional paradigm in radiation biology has been that DNA is the primary target for energy deposition following exposure to ionizing radiation. However, studies focusing on the non-target effects of radiation, i.e. effects occurring in cells not directly exposed to radiation, imply that the target of exposure is larger than what has traditionally been assumed and could have significant implications for radiation health risks. We have conducted an extensive study of the low-LET bystander effect including multiple cell lines and endpoints and various radiation sources and exposure scenarios. In no instance do we see evidence of a low-LET induced bystander effect. However, direct comparison for alpha particle exposure showed a statistically significant media transfer bystander effect for high-LET but not for low-LET radiation. From our results it is evident that there are many confounding factors mitigating bystander responses as reported in the literature and for the cell lines we studied that there is a LET dependence for the observed responses. Our observations reflect the inherent variability in biological systems and the difficulties in extrapolating from in vitro models to radiation risks in humans.

  8. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells.

    PubMed

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

    2013-01-01

    Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent

  9. Real-time Molecular Study of Bystander Effects of Low dose Low LET radiation Using Living Cell Imaging and Nanoparticale Optics

    SciTech Connect

    Natarajan, Mohan; Xu, Nancy R; Mohan, Sumathy

    2013-06-03

    In this study two novel approaches are proposed to investigate precisely the low dose low LET radiation damage and its effect on bystander cells in real time. First, a flow shear model system, which would provide us a near in vivo situation where endothelial cells in the presence of extra cellular matrix experiencing continuous flow shear stress, will be used. Endothelial cells on matri-gel (simulated extra cellular matrix) will be subjected to physiological flow shear (that occurs in normal blood vessels). Second, a unique tool (Single nano particle/single live cell/single molecule microscopy and spectroscopy; Figure A) will be used to track the molecular trafficking by single live cell imaging. Single molecule chemical microscopy allows one to single out and study rare events that otherwise might be lost in assembled average measurement, and monitor many target single molecules simultaneously in real-time. Multi color single novel metal nanoparticle probes allow one to prepare multicolor probes (Figure B) to monitor many single components (events) simultaneously and perform multi-complex analysis in real-time. These nano-particles resist to photo bleaching and hence serve as probes for unlimited timeframe of analysis. Single live cell microscopy allows one to image many single cells simultaneously in real-time. With the combination of these unique tools, we will be able to study under near-physiological conditions the cellular and sub-cellular responses (even subtle changes at one molecule level) to low and very low doses of low LET radiation in real time (milli-second or nano-second) at sub-10 nanometer spatial resolution. This would allow us to precisely identify, at least in part, the molecular mediators that are responsible of radiation damage in the irradiated cells and the mediators that are responsible for initiating the signaling in the neighboring cells. Endothelial cells subjected to flow shear (2 dynes/cm2 or 16 dynes/cm2) and exposed to 0.1, 1 and 10

  10. Who intervenes against homophobic behavior? Attributes that distinguish active bystanders.

    PubMed

    Poteat, V Paul; Vecho, Olivier

    2016-02-01

    Research on homophobic behavior has focused on students engaging in this behavior or students toward whom this behavior is directed. There has been little attention to the large segment of students who observe this behavior, including active bystanders who defend or support students when homophobic behavior occurs. Among 722 high school students (55% female, 87% white, 86% heterosexual), 66.8% had observed at least one instance of homophobic behavior in the past 30 days. Gender (in this case, girls more so than boys), leadership, courage, altruism, justice sensitivity, and number of LGBT friends were associated with engagement in more active bystander behavior in response to observing homophobic behavior. Further, gender, courage, altruism, and number of LGBT friends each made unique contributions in accounting for variability in students' defending behavior in a comprehensive regression model. Findings highlight qualities that interventionists should cultivate in students that could lead to more active bystander engagement against homophobic behavior. PMID:26790700

  11. A Mouse Ear Model for Bystander Studies Induced by Microbeam Irradiation.

    PubMed

    Buonanno, M; Randers-Pehrson, G; Smilenov, L B; Kleiman, N J; Young, E; Ponnayia, B; Brenner, D J

    2015-08-01

    Radiation-induced bystander effects have been observed in vitro and in cell and tissue culture models, however, there are few reported studies showing these effects in vivo. To our knowledge, this is the first reported study on bystander effects induced by microbeam irradiation in an intact living mammal. The mouse ear was used to investigate radiation-induced bystander effects in keratinocytes, utilizing a 3 MeV proton microbeam (LET 13.1 keV/μm) with a range in skin of about 135 μm. Using a custom-designed holder, the ear of an anesthetized C57BL/6J mouse was flattened by gentle suction and placed over the microbeam port to irradiate cells along a 35 μm wide, 6 mm long path. Immunohistochemical analysis of γ-H2AX foci formation in tissue sections revealed, compared to control tissue, proton-induced γ-H2AX foci formation in one of the two epidermal layers of the mouse ear. Strikingly, a higher number of cells than expected showed foci from direct irradiation effects. Although the proton-irradiated line was ~35 μm wide, the average width spanned by γ-H2AX-positive cells exceeded 150 μm. Cells adjacent to or in the epidermal layer opposite the γ-H2AX-positive region did not exhibit foci. These findings validate this mammalian model as a viable system for investigating radiation-induced bystander effects in an intact living organism. PMID:26207682

  12. Action Research Evaluation of Bystander Intervention Training Created by Munche, Stern, and O'Brien

    ERIC Educational Resources Information Center

    Shiflet, Jacqueline H.

    2013-01-01

    This qualitative, appreciative inquiry study was an examination of bystander intervention as related to sexual assault in the military. The purpose of the study was to examine how military personnel and Department of Defense civilian employees reflecting diverse backgrounds perceived the effectiveness of bystander intervention training and sexual…

  13. Bystander's willingness to report theft, physical assault, and sexual assault: the impact of gender, anonymity, and relationship with the offender.

    PubMed

    Nicksa, Sarah C

    2014-01-01

    This research examines bystander willingness to report three different crimes to the police or campus authorities among a college student sample (n = 295). Twelve original vignettes varied anonymity when reporting, bystander's relationship with the offender (friend or stranger), and crime type. A factorial analysis of variance showed that main effects were found for crime type, bystander's gender, and bystander's relationship with the offender; anonymity was not significant. The physical assault was the most likely to be reported (4.47), followed by theft (3.26), and sexual assault (2.36). Women were more likely than men to report each crime type, and bystanders who were good friends of the offender were less likely to report than strangers. No two- or three-way interactions were significant, but a significant four-way interaction indicated that anonymity, relationship with the offender, and bystander's gender predicted willingness to report for the sexual assault scenario. PMID:24142441

  14. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

    PubMed

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-04-30

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy. PMID:25868859

  15. Observed Workplace Incivility toward Women, Perceptions of Interpersonal Injustice, and Observer Occupational Well-Being: Differential Effects for Gender of the Observer

    PubMed Central

    Miner, Kathi N.; Cortina, Lilia M.

    2016-01-01

    The present study examined perceptions of interpersonal injustice as a mediator of the relationship between observed incivility toward women at work and employees' occupational well-being. We also examined gender of the observer as a moderator of these mediational relationships. Using online survey data from 1702 (51% women; 92% White) employees, results showed that perceptions of injustice partially mediated the relationship between observed incivility toward women and job satisfaction, turnover intentions, and organizational trust. Men reported greater perceptions of injustice than did women the more they observed the uncivil treatment of women at work, and the indirect effects of observed incivility toward women on well-being were stronger for men compared to women. Observed incivility toward women also had direct relationships with the occupational well-being outcomes over and above the impact mediated through injustice, particularly for women. Specifically, observing incivility toward female coworkers directly related to lowered job satisfaction and perceptions of safety for female bystanders. In addition, although both male and female bystanders reported heightened turnover intentions and lowered trust in the organization with higher levels of observed incivility toward women, these relationships were stronger for female than male observers. Our findings both replicate and extend past research on vicarious workplace incivility toward women. PMID:27242558

  16. Observed Workplace Incivility toward Women, Perceptions of Interpersonal Injustice, and Observer Occupational Well-Being: Differential Effects for Gender of the Observer.

    PubMed

    Miner, Kathi N; Cortina, Lilia M

    2016-01-01

    The present study examined perceptions of interpersonal injustice as a mediator of the relationship between observed incivility toward women at work and employees' occupational well-being. We also examined gender of the observer as a moderator of these mediational relationships. Using online survey data from 1702 (51% women; 92% White) employees, results showed that perceptions of injustice partially mediated the relationship between observed incivility toward women and job satisfaction, turnover intentions, and organizational trust. Men reported greater perceptions of injustice than did women the more they observed the uncivil treatment of women at work, and the indirect effects of observed incivility toward women on well-being were stronger for men compared to women. Observed incivility toward women also had direct relationships with the occupational well-being outcomes over and above the impact mediated through injustice, particularly for women. Specifically, observing incivility toward female coworkers directly related to lowered job satisfaction and perceptions of safety for female bystanders. In addition, although both male and female bystanders reported heightened turnover intentions and lowered trust in the organization with higher levels of observed incivility toward women, these relationships were stronger for female than male observers. Our findings both replicate and extend past research on vicarious workplace incivility toward women. PMID:27242558

  17. The Men's Program: does it impact college men's self-reported bystander efficacy and willingness to intervene?

    PubMed

    Langhinrichsen-Rohling, Jennifer; Foubert, John D; Brasfield, Hope M; Hill, Brent; Shelley-Tremblay, Shannon

    2011-06-01

    This study considered whether a rape prevention program could reduce men's rape myth acceptance, enhance the perceived effectiveness of college men's bystander behavior, and increase men's willingness to intervene as bystanders in potentially dangerous situations. As predicted, college men who experienced The Men's Program significantly increased their self-reported willingness to help as a bystander and their perceived bystander efficacy in comparison to college men who experienced the comparison condition. Men's Program participants also significantly decreased their self-reported rape myth acceptance in comparison with comparison condition participants. The college policy and rape prevention program planning implications of these findings are discussed. PMID:21571743

  18. Bystander Macrophage Apoptosis after Mycobacterium tuberculosis H37Ra Infection▿

    PubMed Central

    Kelly, Deirdre M.; ten Bokum, Annemieke M. C.; O'Leary, Seonadh M.; O'Sullivan, Mary P.; Keane, Joseph

    2008-01-01

    Human macrophages infected with Mycobacterium tuberculosis may undergo apoptosis. Macrophage apoptosis contributes to the innate immune response against M. tuberculosis by containing and limiting the growth of mycobacteria and also by depriving the bacillus of its niche cell. Apoptosis of infected macrophages is well documented; however, bystander apoptosis of uninfected macrophages has not been described in the setting of M. tuberculosis. We observed that uninfected human macrophages underwent significant bystander apoptosis 48 and 96 h after they came into contact with macrophages infected with avirulent M. tuberculosis. The bystander apoptosis was significantly greater than the background apoptosis observed in uninfected control cells cultured for the same length of time. There was no evidence of the involvement of tumor necrosis factor alpha, Fas, tumor necrosis factor-related apoptosis-inducing ligand, transforming growth factor β, Toll-like receptor 2, or MyD88 in contact-mediated bystander apoptosis. This newly described phenomenon may further limit the spread of M. tuberculosis by eliminating the niche cells on which the bacillus relies. PMID:17954721

  19. Prosocial Bystander Behavior in Bullying Dynamics: Assessing the Impact of Social Capital.

    PubMed

    Evans, Caroline B R; Smokowski, Paul R

    2015-12-01

    Individuals who observe a bullying event, but are not directly involved as a bully or victim, are referred to as bystanders. Prosocial bystanders are those individuals who actively intervene in bullying dynamics to support the victim and this prosocial behavior often ends the bullying. The current study examines how social capital in the form of social support, community engagement, mental health functioning, and positive school experiences and characteristics is associated with the likelihood of engaging in prosocial bystander behavior in a large sample (N = 5752; 51.03% female) of racially/ethnically diverse rural youth. It was hypothesized that social capital would be associated with an increased likelihood of engaging in prosocial bystander behavior. Following multiple imputation, an ordered logistic regression with robust standard errors was run. The hypothesis was partially supported and results indicated that social capital in the form of friend and teacher support, ethnic identity, religious orientation, and future optimism were significantly associated with an increased likelihood of engaging in prosocial bystander behavior. Contrary to the hypothesis, a decreased rate of self-esteem was significantly associated with an increased likelihood of engaging in prosocial bystander behavior. The findings highlight the importance of positive social relationships and community engagement in increasing prosocial bystander behavior and ultimately decreasing school bullying. Implications were discussed. PMID:26251101

  20. Are Synchronized Changes in Connexin-43 and Caveolin-3 a Bystander Effect in a Phoneutria nigriventer Venom Model of Blood-Brain Barrier Breakdown?

    PubMed

    Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; Rocha, Thalita; Kalapothakis, Evanguedes; da Cruz-Höfling, Maria Alice

    2016-08-01

    Upregulation of caveolin-3 (Cav-3) or connexin-43 (Cx43) in astrocytes has been associated with important brain pathologies. We used Phoneutria nigriventer spider venom (PNV), which induces blood-brain barrier breakdown in rats, in order to investigate Cav-3 and Cx43 expression in the cerebellum over critical periods of rat envenomation. By immunofluorescence, western blotting (WB), and transmission electron microscopy (TEM), we assessed changes at 1, 2, 5, 24, and 72 h post-venom. WB showed immediate increases in Cav-3 and Cx43 at 1 h (interval of greatest manifestations of envenomation) that persisted at 5 h (when there were signs of recovery) and peaked at 24 h when no signs of envenomation were detectable. At 2 and 72 h, Cav-3 was downregulated and Cx43 had returned to baseline. PNV markedly intensified Cx43 in molecular, Purkinje and granular layers and Cav-3 in astrocytes whose colocalization to increased GFAP suggests interaction between reactive astrogliosis and Cav-3 upregulation. TEM showed swollen perivascular astrocytic end-feet and synaptic contact alterations that had generally resolved by 72 h. It is uncertain whether such PNV-induced synchronized changes are an interactive effect between Cav-3 and Cx43, or a bystander effect. Evidences indicate that Cav-3 downregulation coupled to Cx43 return to baseline at 72 h when no signs of envenomation were visible, suggesting homeostasis reestablishment. This experimental model is relevant to studying mechanisms involved in neurological disorders associated with Cav-3 overexpression. PMID:27067308

  1. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation.

    PubMed

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  2. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

    NASA Astrophysics Data System (ADS)

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  3. Moral Disengagement among Bystanders to School Bullying

    ERIC Educational Resources Information Center

    Obermann, Marie-Louise

    2011-01-01

    This study examined the use of moral disengagement among children indirectly involved in bullying (bystanders). A sample of Danish adolescents (N = 660, M age 12.6 years) were divided into four groups depending on their bystander status: (a) outsiders, who did not experience bullying among their peers; (b) defenders, who were likely to help the…

  4. Effects of Low-Dose Alpha-Particle Irradiation in Human Cells: The Role of Induced Genes and the Bystander Effect. Final Technical Report (9/15/1998-5/31/2005)

    SciTech Connect

    Little, John B.

    2013-09-17

    This grant was designed to examine the cellular and molecular mechanisms for the bystander effect of radiation (initially described in this laboratory) whereby damage signals are passed from irradiated to non-irradiated cells in a population. These signals induce genetic effects including DNA damage, mutations and chromosomal aberrations in the nonirradiated cells. Experiments were carried out in cultured mammalian cells, primarily human diploid cells, irradiated with alpha particles. This research resulted in 17 publications in the refereed literature and is described in the Progress Report where it is keyed to the publication list. This project was initiated at the Harvard School of Public Health (HSPH) and continued in collaboration with students/fellows at Colorado State University (CSU) and the New Jersey Medical School (NJMS).

  5. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    PubMed Central

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  6. Morbidity among bystanders of bullying behavior at school: concepts, concerns, and clinical/research issues.

    PubMed

    Rivers, Ian

    2012-01-01

    The role of the bystander is not one that is easily understood in the anti-bullying literature. Roles within the unofficial hierarchy of the school-yard and playground overlap considerably, and each role has its own social dynamic that brings with it a shifting behavioral landscape that affects every student. In this article, the mental health correlates of three categories of bystander are explored: the co-victim, the isolate, and the confederate. Each category of bystander has its own characterizations and mental health correlates. Reports of post-traumatic stress, internalized hostility, substance use, and suicide ideation are discussed with reference to studies involving witnesses of family abuse, community and school violence as well as bullying. It is argued that bystanders are the key to challenging bullying in schools, and their mental health and well-being is pivotal to the effectiveness of anti-bullying interventions. PMID:22909907

  7. Speculations about Bystander and Biophotons.

    PubMed

    Sanders, Charles L

    2014-12-01

    Mothersill and many others during the last hundred years have shown that cells and now whole animals may communicate with each other by electromagnetic waves called biophotons. This would explain the source of the bystander phenomena. These ultra-weak photons are coherent, appear to originate and concentrate in DNA of the cell nucleus and rapidly carry large amounts of data to each cell and to the trillions of other cells in the human body. The implications of such a possibility can be wonderfully important. PMID:25552952

  8. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury

    PubMed Central

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H.R.; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo

    2015-01-01

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding “bystander” cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca2+-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy. PMID:25868859

  9. L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation

    PubMed Central

    Kummer, Mirko; Mühl-Zürbes, Petra; Drassner, Christina; Daniel, Christoph; Klewer, Monika; Steinkasserer, Alexander

    2015-01-01

    ABSTRACT Mature dendritic cells (mDCs) are known as the most potent antigen-presenting cells (APCs) since they are also able to prime/induce naive T cells. Thus, mDCs play a pivotal role during the induction of antiviral immune responses. Remarkably, the cell surface molecule CD83, which was shown to have costimulatory properties, is targeted by herpes simplex virus 1 (HSV-1) for viral immune escape. Infection of mDCs with HSV-1 results in downmodulation of CD83, resulting in reduced T cell stimulation. In this study, we report that not only infected mDCs but also uninfected bystander cells in an infected culture show a significant CD83 reduction. We demonstrate that this effect is independent of phagocytosis and transmissible from infected to uninfected mDCs. The presence of specific viral proteins found in these uninfected bystander cells led to the hypothesis that viral proteins are transferred from infected to uninfected cells via L particles. These L particles are generated during lytic replication in parallel with full virions, called H particles. L particles contain viral proteins but lack the viral capsid and DNA. Therefore, these particles are not infectious but are able to transfer several viral proteins. Incubation of mDCs with L particles indeed reduced CD83 expression on uninfected bystander DCs, providing for the first time evidence that functional viral proteins are transmitted via L particles from infected mDCs to uninfected bystander cells, thereby inducing CD83 downmodulation. IMPORTANCE HSV-1 has evolved a number of strategies to evade the host's immune system. Among others, HSV-1 infection of mDCs results in an inhibited T cell activation caused by degradation of CD83. Interestingly, CD83 is lost not only from HSV-1-infected mDCs but also from uninfected bystander cells. The release of so-called L particles, which contain several viral proteins but lack capsid and DNA, during infection is a common phenomenon observed among several viruses, such

  10. Increased Frequency of Spontaneous Neoplastic Transformation in Progeny of Bystander Cells from Cultures Exposed to Densely Ionizing Radiation

    PubMed Central

    Buonanno, Manuela; de Toledo, Sonia M.; Azzam, Edouard I.

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  11. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

    PubMed

    Buonanno, Manuela; de Toledo, Sonia M; Azzam, Edouard I

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  12. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance

    PubMed Central

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc- (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  13. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance.

    PubMed

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc(-) (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  14. An Online Bystander Intervention Program for the Prevention of Sexual Violence

    PubMed Central

    Kleinsasser, Anne; Jouriles, Ernest N.; McDonald, Renee; Rosenfield, David

    2014-01-01

    Objective Because of its high prevalence and serious consequences for victims, sexual violence is a significant problem on college campuses. Sexual assault prevention programs based on the bystander intervention model have been shown to be effective; however, current programs are limited in terms of ease of distribution. To address this issue, we developed and evaluated “Take Care,” an online bystander intervention program. To our knowledge, this is the first empirical evaluation of an online bystander intervention program designed to prevent sexual violence. Method Ninety-three participants (80.6% female, 19.4% male) recruited from social psychology classes at a mid-size university were randomly assigned to view one of two online programs: Take Care or a control program on study skills. Before viewing the programs, participants completed measures of bystander behaviors and feelings of efficacy for performing such behaviors. Measures were administered again post-intervention and at a two-month follow-up assessment. Results Participants who viewed Take Care reported greater efficacy for engaging in bystander behaviors at post-treatment and two months following treatment, compared to those who viewed the control program. In addition, participants who viewed Take Care reported performing relatively more bystander behaviors for friends at the two-month follow-up assessment, compared to participants who viewed the control program. Conclusions These results suggest that sexual violence prevention programs may be effectively adapted to an online format. PMID:26240776

  15. Genetic factors influencing bystander signaling in murine bladder epithelium after low-dose irradiation in vivo.

    PubMed

    Mothersill, Carmel; Lyng, Fiona; Seymour, Colin; Maguire, Paula; Lorimore, Sally; Wright, Eric

    2005-04-01

    Radiation-induced bystander effects occur in cells that are not directly hit by radiation tracks but that receive signals from hit cells. They are well-documented in vitro consequences of low-dose exposure, but their relevance to in vivo radiobiology is not established. To investigate the in vivo production of bystander signals, bladder explants were established from two strains of mice known to differ significantly in both short-term and long-term radiation responses. These were investigated for the ability of 0.5 Gy total-body irradiation in vivo to induce production of bystander signals in bladder epithelium. The studies demonstrate that irradiated C57BL/6 mice, but not CBA/Ca mice, produce bystander signals that induce apoptosis and reduce clonogenic survival in reporter HPV-G-transfected keratinocytes. Transfer of medium from explants established from irradiated animals to explants established from unirradiated animals confirmed these differences in bladder epithelium. The responses to the in vivo-generated bystander signal exhibit genotypic differences in calcium signaling and also in signaling pathways indicative of a major role for the balance of pro-apoptosis and anti-apoptosis proteins in determining the overall response. The results clearly demonstrate the in vivo induction of bystander signals that are strongly influenced by genetic factors and have implications for radiation protection, medical imaging, and radiotherapy. PMID:15799694

  16. Challenge and opportunity in evaluating a diffusion-based active bystanding prevention program: Green Dot in high schools.

    PubMed

    Cook-Craig, Patricia G; Coker, Ann L; Clear, Emily R; Garcia, Lisandra S; Bush, Heather M; Brancato, Candace J; Williams, Corrine M; Fisher, Bonnie S

    2014-10-01

    Increasing attention has recently been paid to the development of prevention programs designed to actively engage bystanders in prevention efforts to reduce the risk of sexual and dating violence; yet, few evaluations have been conducted. Our proposed plan to rigorously evaluate a randomized intervention trial of the Green Dot bystander program as it is implemented in high schools across Kentucky is presented. We highlight the value of measuring violence victimization and perpetration outcomes, capturing actual and observed student bystander behaviors, and testing the diffusion of Green Dot training through students' social networks. PMID:25255794

  17. Do Sexual Assault Bystander Interventions Change Men's Intentions? Applying the Theory of Normative Social Behavior to Predicting Bystander Outcomes.

    PubMed

    Mabry, Amanda; Turner, Monique Mitchell

    2016-01-01

    The high prevalence of sexual assault on college campuses has led to the implementation of health communication programs to prevent sexual assault. A few novel programs focus on primary prevention by targeting social norms related to gender and masculinity among men through bystander intervention. Guided by the theory of normative social behavior, this study sought to examine the relative effect of campaigns communicating positive versus negative injunctive norms and the interaction between exposure to such campaign messages and perceived descriptive norms and relevant cognitive moderators (e.g., outcome expectations, injunctive norms, group identity, ego involvement) among men. A 2 (high/low descriptive norms) × 2 (high/low moderator) × 3 (public service announcement) independent groups quasi-experimental design (N = 332) was used. Results indicated that messages communicating positive injunctive norms were most effective among men who were least likely to engage in bystander intervention. Furthermore, descriptive norms played a significant role in behavioral intentions, such that those with stronger norms were more likely to report intentions to engage in bystander behaviors in the future. Similarly, the moderators of aspiration, injunctive norms, social approval, and ego involvement had a significant positive effect on behavioral intentions. These findings have important implications for future message design strategy and audience segmentation. PMID:26716826

  18. Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells

    PubMed Central

    Bryan, Ruth A; Jiang, Zewei; Morgenstern, Alfred; Bruchertseifer, Frank; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Aim Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander mammalian cells. Materials & methods Heat-killed C. neoformans bound to anticapsular antibodies, unlabeled or labeled with the β-emitter rhenium-188 (16.9-h half-life) or the α-emitter bismuth-213 (46-min half-life), was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-terazolium-5-carboxanilide and nitric oxide production were measured. Results The J774.16 and Chinese hamster ovary cells maintained membrane integrity, viability and metabolic activity following exposure to radiolabeled C. neoformans. Conclusion RIT of C. neoformans is a selective therapy with minimal effects on host cells and these results are consistent with observations that RIT-treated mice with cryptococcal infection lacked RIT-related pathological changes in lungs and brain tissues. PMID:24020737

  19. Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others

    PubMed Central

    van Bommel, Marco; van Prooijen, Jan-Willem; Elffers, Henk; Van Lange, Paul A. M.

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors of bars in Amsterdam to join our study at a secluded spot at the bar. We manipulated bystander presence, and at the end of the study, we measured alcohol consumption. When participants took their seats, the experimenter dropped some items. We measured how many items were picked up and how quickly participants engaged in helping. Results revealed that alcohol did not influence the bystander effect in terms of the amount of help given. But importantly, it did influence the bystander effect in terms of response times: people who consumed alcohol actually came to aid faster in the presence of others. PMID:26903929

  20. Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma.

    PubMed

    Shareef, Mohammed M; Cui, Nuan; Burikhanov, Ravshan; Gupta, Seema; Satishkumar, Sabapathi; Shajahan, Shahin; Mohiuddin, Mohammed; Rangnekar, Vivek M; Ahmed, Mansoor M

    2007-12-15

    In the present study, ionizing radiation (IR)-induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-alpha (TNF-alpha) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-alpha. In H460 cells, significant release of TNF-related apoptosis-inducing ligand (TRAIL), but not TNF-alpha, was observed in response to IR, RCM exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished clonogenic inhibition. Mechanistically, TNF-alpha present in RCM of A549 was found to mediate nuclear factor-kappaB (NF-kappaB) translocation to nucleus, whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells but not in H460 cells. A significant decrease in RCM-mediated apoptosis was observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR-1(-/-) mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander responses in A549 may be dependent on the EGR-1 function and its target gene TNF-alpha. These findings show that the reduced bystander response in A549 cells is due to activation of NF-kappaB signaling by TNF-alpha, whereas enhanced response to IR-induced bystander signaling in H460 cells was due to release of TRAIL associated with nuclear translocation of PAR-4. PMID:18089811

  1. Injection of Resperpine into Zebrafish, Prevents Fish to Fish Communication of Radiation-Induced Bystander Signals: Confirmation in Vivo of a Role for Serotonin in the Mechanism

    PubMed Central

    Saroya, Rohin; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2009-01-01

    Serotonin (5-HT) has been implicated as a potential modulator of the bystander effect in cell cultures. To assess the relevance of serotonin in vivo experiments were done with the zebrafish (Danio rerio). This species, when irradiated, transmits bystander signals to non-irradiated fish. The animals were injected with reserpine, an inhibitor of serotonin at a dose of 80mg/kg of body mass. The results show that reserpine treated fish had only 27% of the serotonin in non-treated fish. Skin tissue samples were collected from the fish and assayed for bystander signal production using a reporter bioassay. Reserpine prevented the production and communication of signals between fish. Intracellular calcium flux, identified as a bystander response in the reporter cells confirmed this. Medium harvested from tissues of X-rayed fish and their bystanders, showed an oscillating pattern of calcium flux. Samples from X-rayed fish pretreated with reserpine produced a chaotic pattern of random fluctuations in the reporter cells, while their bystander fish led to increased calcium, but no oscillations. These results suggest that 5-HT is involved in bystander signalling in zebrafish, and by decreasing the amount of available 5-HT the bystander effect can be blocked. PMID:20877486

  2. BYSTANDER RESPONSES IN THREE-DIMENSIONAL CULTURES CONTAINING RADIOLABELLED AND UNLABELLED HUMAN CELLS

    PubMed Central

    Pinto, M.; Azzam, E. I.; Howell, R. W.

    2010-01-01

    Research on the radiation-induced bystander effect has been carried out mainly in 2-D tissue culture systems. This study uses a 3-D model, wherein apparently normal human diploid fibroblasts (AG1522) are grown in a carbon scaffold, to investigate the induction of a G1 checkpoint in bystander cells present alongside radiolabelled cells. Cultures were simultaneously pulse-labelled with 3H-deoxycytidine (3HdC) to selectively irradiate a minor fraction of cells, and bromodeoxyuridine (BrdU) to identify the radiolabelled cells. After thorough washing of cultures, iododeoxyuridine (IdU) was administered to detect proliferating bystander cells. The cultures were harvested at various times thereafter, and cells were reacted with two monoclonal antibodies specific to IdU/BrdU or BrdU, respectively, stained with propidium iodide, and subjected to multi-parameter flow cytometry. Cell-cycle progression was followed in radiolabelled cells (BrdU+) that were chronically irradiated by low energy beta particles emitted by DNA-incorporated 3H, and in unlabelled bystander cells (BrdU−) by a flow cytometry based cumulative labelling index assay. As expected, radiolabelled cells were delayed, in a dose-dependent manner, in G2 and subsequently G1. No delay occurred in progression of bystander cells through G1, when the labelled cells were irradiated at dose rates up to 0.32 Gy h−1. PMID:17185313

  3. Predicting Bystander Behavior to Prevent Sexual Assault on College Campuses: The Role of Self-Efficacy and Intent.

    PubMed

    McMahon, Sarah; Peterson, N Andrew; Winter, Samantha C; Palmer, Jane E; Postmus, Judy L; Koenick, Ruth Anne

    2015-09-01

    Bystander intervention has been increasingly applied to prevent sexual violence on college campuses. Its underlying theory assumes unidirectional relationships between variables, predicting that bystander behaviors (i.e., actions taken to intervene in sexual violence situations) will be influenced by bystander intentions (BI; i.e., likelihood to intervene in the future), which in turn will be affected by bystander efficacy (BE; i.e., confidence to intervene). One question for theory is whether a reciprocal relationship exists between BI and BE. We used structural equation modeling (SEM) with longitudinal data to test unidirectional and reciprocal causal relations between BI and BE. Participants (n = 1390) were students at a northeastern US university. Four models were examined using SEM: (1) a baseline model with autoregressive paths; (2) a model with autoregressive effects and BI predicting future BE; (3) a model with autoregressive effects and BE predicting future BI; and, (4) a fully cross-lagged model. Results indicated that reciprocal causality was found to occur between BI and BE. In addition, a final model demonstrated indirect effects of a bystander intervention program on bystander behaviors through both BI and BE at different time points. Implications for theory and practice are described, and directions for future research discussed. PMID:26194588

  4. Rethinking the bystander role in school violence prevention.

    PubMed

    Stueve, Ann; Dash, Kimberly; O'Donnell, Lydia; Tehranifar, Parisa; Wilson-Simmons, Renée; Slaby, Ronald G; Link, Bruce G

    2006-01-01

    Public concerns about school shootings and safety draw attention to the role bystanders can play in preventing school violence. Although school violence prevention plans are often required, there is little guidance about whether these should address the roles of bystanders and what actions bystanders should take in different circumstances, from more common instances of bullying and fighting to rare, but potentially lethal, threats and use of weapons. Literature pertaining to bystanders is reviewed and applied to the school setting. The definition of bystander is expanded, including parents, teachers, and other school staff as well as youths and those who have information about potential violence as well as those who witness its occurrence. Barriers preventing bystanders from taking positive actions are discussed. The authors call on health promotion researchers and practitioners to work with school communities to identify norms, attitudes, and outcome expectancies that shape bystander behaviors to inform prevention efforts. PMID:16410428

  5. Mutations in Succinate Dehydrogenase Subunit C Increase Radiosensitivity and Bystander Responses

    NASA Astrophysics Data System (ADS)

    Zhou, Hongning; Hei, Tom K.

    Although radiation-induced bystander effect is well studied in the past decade, the precise mech-anisms are still unclear. It is likely that a combination of pathways involving both primary and secondary signaling processes is involved in producing a bystander effect. There is recent evidence that mitochondria play a critical role in bystander responses. Recently studies found that a mutation in succinate dehydrogenese subunit C (SDHC), an integral membrane protein in complex II of the electron transport chain, resulted in increased superoxide, oxidative stress, apoptosis, tumorigenesis, and genomic instability, indicating that SDHC play a critical role in maintaining mitochondrial function. In the present study, using Chinese hamster fibroblasts (B1 cells) and the mutants (B9 cells) containing a single base substitution that produced a premature stop codon resulting in a 33-amino acid COOH-terminal truncation of the SDHC protein, we found that B9 cells had an increase in intracellular superoxide content, nitric oxide species, and mitochondrial membrane potential when compared with wild type cells. After irradiated with a grade of doses of gamma rays, B9 cells show an increased radiosensitivity, especially at high doses. The HPRT- mutant yield after gamma-ray irradiation in B9 cells was significantly higher than that of B1 cells. A single, 3Gy dose of gamma-rays increased the background mutant level by more than 4 fold. In contrast, the mutant induction was less than 2 fold in B1 cells. In addition, B9 cells produced a higher bystander mutagenesis after alpha particle irradiation than the B1 cells. Furthermore, pretreated with carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), a nitric oxide scavenger, significantly decreased the bystander effect. Our findings demonstrate that a mutation in SDHC increases radiosensitivity in both directly irradiated cells and in neighboring bystander cells, and mito-chondrial function play an essential role in

  6. That's What Friends Are For: Bystander Responses to Friends or Strangers at Risk for Party Rape Victimization.

    PubMed

    Katz, Jennifer; Pazienza, Rena; Olin, Rachel; Rich, Hillary

    2015-10-01

    The present research examined bystander responses to potential party rape scenarios involving either a friend or a stranger at risk. Undergraduate students (N = 151) imagined attending a party and seeing a man lead an intoxicated woman (friend or stranger) into a bedroom. After random assignment to conditions, participants reported on intentions to help, barriers to helping, victim blame, and empathic concern. As expected, based on their shared social group membership, bystanders intended to offer more help to friends than to strangers. Bystanders also reported more personal responsibility to help and more empathic concern when the potential victim was a friend rather than stranger. Observing a friend versus stranger at risk did not affect audience inhibition or perceived victim blame. Compared with women, men reported more blame and less empathic concern for potential victims. However, there were no gender differences in bystander intent to help or barriers to helping. In multivariate analyses, both responsibility to help and empathic concern for the potential victim uniquely predicted bystanders' intent to help a woman at risk for party rape. Results suggest that promoting social identification with peers at risk could increase bystander intervention. PMID:25349015

  7. Low-LET Bystander Responses in Gap Junction Null Human Colon Carcinoma Cells (RK036)

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Morgan, William F.

    2006-10-01

    Combined with sensitive molecular techniques, the microbeam has proven extremely useful in studying radiation biology. This technology allows individual cells, or selected groups of cells, to be irradiated at specific doses and dose rates. Such capabilities lend themselves well to studies of low dose responses, delayed and non-targeted bystander effects of radiation. High-linear energy transfer (LET) microbeams mimic heavy energetic particles such as the ?-particles associated with radon exposure and have been used in numerous biological studies. Several low-LET microbeams have also been developed. One such low-LET microbeam, developed at the Pacific Northwest National Laboratory and currently located at the University of Maryland Radiation Oncology Research Laboratory, uses a variable energy electron source to mimic low-LET radiation and allows observation of how x-rays and ?-rays affect mammalian cells.

  8. Assessing Bystander Behavior Intentions Toward Friends to Prevent Dating Violence: Development of the Bystander Behavior Intentions-Friends Scale Through Concept Mapping and Exploratory Factor Analysis.

    PubMed

    Borsky, Amanda E; McDonnell, Karen; Rimal, Rajiv N; Turner, Monique

    2016-01-01

    Bystander behavior interventions aim to reduce violence by encouraging individuals to intervene in a safe and effective manner when they hear or see circumstances that could lead to violence. This study used a participatory-based approach to develop a 9-item scale to measure bystander behaviors to prevent dating violence among friends. Predominantly, female students (N = 37) on a college campus in the Mid-Atlantic region of the United States were asked to define bystander behaviors. Responses were thematically sorted and ranked according to importance in preventing dating violence and feasibility by 12 participants. Psychometric testing of intentions to perform the behavior was done based on responses from an additional 288 respondents. Exploratory factor analysis was used to examine whether bystander behaviors directed at friends to prevent dating violence was a uni- or multidimensional construct, which has not been done to date in the available literature. Results demonstrated a unidimensional factor structure with strong factor loadings (above .71) and internal consistency (Cronbach's alpha .92); items focused on primary and secondary prevention behaviors toward friends. These findings provide a reliable and single construct scale to assess college-age women's response to witnessing the victimization of a friend. These findings can facilitate future program evaluations. PMID:26822267

  9. No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

    2013-02-01

    A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

  10. Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells.

    PubMed

    Moon, Ho Suck; Yang, Joo-Sung

    2006-02-28

    The major event in human immunodeficiency virus type 1 (HIV-1) infection is the death of many cells related to host immune response. The demise of these cells is normally explained by cell suicide mechanism, apoptosis. Interestingly, the decrease in the number of immune cells, such as non-CD4(+) cells as well as CD4(+) T cells, in HIV infection usually occurs in uninfected bystander cells, not in directly infected cells. It has, therefore, been suggested that several soluble factors, including viral protein R (Vpr), are released from the infected cells and induce the death of bystander cells. Some studies show that Vpr interacts directly with adenine nucleotide translocator (ANT) to induce mitochondrial membrane permeabilization (MMP). The MMP results in release of some apoptogenic factors such as cytochrome-c (cyt-c) and apoptosis-inducing factor (AIF). Vpr also has indirect effect on mitochondria through enhancing the level of caspase-9 transcription and suppressing nuclear factor-kappa B (NF-kB). The involvement of p53 in Vpr-induced apoptosis remains to be studied. On the other hand, low level of Vpr expression has anti-apoptotic effect, whereas it's high level of expression induces apoptosis. Extracellular Vpr also exhibits cytotoxicity to uninfected bystander cells through apoptotic or necrotic mechanism. The facts that Vpr has cytotoxic effect on both infected cells and bystander cells, and that it exhibits both pro- and anti-apoptotic activity may explain its role in viral survival and disease progression. PMID:16511342

  11. Bystander T cells participate in specific response to cockroach antigen (CR) in vitro.

    PubMed

    Walters, C S; Tackey, R N; Reece, E; Paluvoi, S

    2003-02-01

    Allergic reactions due to whole body, body parts and fecal products of cockroach (CR) are characterized by inflammatory reaction that may lead to symptoms of rhinitis or asthma in atopic individuals. Although the majority of T cells at the site of CR hypersensitivity are not antigen specific, the cellular subset and cytokine receptors that participate and control the outcome of the reaction have not been fully studied. In this study, we have used fluorescent activated cell sorter (FACS) analysis to characterize the activation marker and cytokine profile of antigen specific and bystander T cells after in vitro stimulation of peripheral blood lymphocytes with whole body extract of CR antigen. There was significant enhancement of CD69 on blast and bystander T cells in all atopic subjects compared to non-atopics. Both antigen specific and bystander T cells showed increased expression of HLA-DR, CD25 and CD71 in 9 of 11 atopic patients compared to control. There was also an increase in CD45RA+ and a decrease in CD45RO+ cells following antigen stimulation. These results correlated with the increase in the early apoptotic cells observed in patients as measured by Annexin V stain. Our data revealed that there was no difference in the expression of CD95 in both stimulated and bystander T cells. However, there was enhancement of FasL by CR antigen, suggesting that the increased apoptosis that was observed was probably due to the Fas/FasL interaction. Positive intracellular IL2, IL-4 and IFN-gamma in T cells were observed in only the antigen specific blast cells in 83% of patients studied. These results suggest interplay of memory T cell response, apoptosis, and activated bystander T cells activities in maintaining cellular homeostasis during allergic reaction in cockroach sensitive atopic subjects. PMID:12722946

  12. Bystanders, parcelling, and an absence of trust in the grooming interactions of wild male chimpanzees

    PubMed Central

    Kaburu, Stefano S. K.; Newton-Fisher, Nicholas E.

    2016-01-01

    The evolution of cooperation remains a central issue in socio-biology with the fundamental problem of how individuals minimize the risks of being short-changed (‘cheated’) should their behavioural investment in another not be returned. Economic decisions that individuals make during interactions may depend upon the presence of potential partners nearby, which offers co operators a temptation to defect from the current partner. The parcelling model posits that donors subdivide services into parcels to force cooperation, and that this is contingent on opportunities for defection; that is, the presence of bystanders. Here we test this model and the effect of bystander presence using grooming interactions of wild chimpanzees. We found that with more bystanders, initiators gave less grooming at the beginning of the bout and were more likely to abandon a grooming bout, while bouts were less likely to be reciprocated. We also found that the groomer’s initial investment was not higher among frequent groomers or stronger reciprocators, suggesting that contrary to current assumptions, grooming decisions are not based on trust, or bonds, within dyads. Our work highlights the importance of considering immediate social context and the influence of bystanders for understanding the evolution of the behavioural strategies that produce cooperation. PMID:26856371

  13. Participation in High School Sports and Bystander Intentions, Efficacy to Intervene, and Rape Myth Beliefs.

    PubMed

    McMahon, Sarah

    2015-10-01

    Debate exists as to whether male athletes are more prone to commit acts of sexual violence and maintain problematic attitudes about sexual assault. To contribute to the literature on this relationship, this study posed the following research questions: (1) Do those students who participated in high school sports and those who did not differ significantly in their attitudes about sexual violence and willingness to intervene as a bystander? Do these differ among types of rape myths and bystander intervention situations? (2) Within a group of athletes, are there significant differences by gender or type of sport (contact sport vs. non-contact?) To answer these questions, surveys were analyzed with a sample of recent high school graduates the summer before entering college (N = 3,588). Results indicate that there were only minor differences between those students who participated in high school varsity sports and those who did not. Students who participated in sports had greater acceptance of three out of five types of rape myths, and less willingness to intervene with perpetrators after an assault; however, the effect sizes were small. There were no significant differences for bystander efficacy. The interaction between sport and gender was significant, but contact sport was not. The findings suggest that there may be aspects of male athletic participation in sports that needs to be addressed, yet there also exists the potential for engaging athletes as leaders who can act as prosocial bystanders. PMID:25392384

  14. Intrachromosomal Changes and Genomic Instability in Site-Specific Microbeam-Irradiated and Bystander Human-Hamster Hybrid Cells

    PubMed Central

    Hu, Burong; Grabham, Peter; Nie, Jing; Balajee, Adayabalam S.; Zhou, Hongning; Hei, Tom K.; Geard, Charles R.

    2012-01-01

    Exposure to ionizing radiation may induce a heritable genomic instability phenotype that results in a persisting and enhanced genetic and functional change among the progeny of irradiated cells. Since radiation-induced bystander effects have been demonstrated with a variety of biological end points under both in vitro and in vivo conditions, this raises the question whether cytoplasmic irradiation or the radiation-induced bystander effect can also lead to delayed genomic instability. In the present study, we used the Radiological Research Accelerator Facility charged-particle microbeam for precise nuclear or cytoplasmic irradiation. The progeny of irradiated and the bystander human hamster hybrid (AL) cells were analyzed using multicolor banding (mBAND) to examine persistent chromosomal changes. Our results showed that the numbers of metaphase cells involving changes of human chromosome 11 (including rearrangement, deletion and duplication) were significantly higher than that of the control in the progeny of both nuclear and cytoplasmic targeted cells. These chromosomal changes could also be detected among the progeny of bystander cells. mBAND analyses of clonal isolates from nuclear and cytoplasm irradiations as well as the bystander cell group showed that chromosomal unstable clones were generated. Analyses of clonal stability after long-term culture indicated no significant change in the number of unstable clones for the duration of culture in each irradiated group. These results suggest that genomic instability that is manifested after ionizing radiation exposure is not dependent on direct damage to the cell nucleus. PMID:22077336

  15. Measuring Bystander Attitudes and Behavior to Prevent Sexual Violence

    ERIC Educational Resources Information Center

    McMahon, Sarah; Allen, Christopher T.; Postmus, Judy L.; McMahon, Sheila M.; Peterson, N. Andrew; Lowe Hoffman, Melanie

    2014-01-01

    Objective: The purpose of this study is to further investigate the factor structure and strength of the Bystander Attitude Scale-Revised and Bystander Behavior Scale-Revised (BAS-R and BBS-R). Participants: First-year students (N = 4,054) at a large public university in the Northeast completed a survey in 2010 as part of a larger longitudinal…

  16. Implications for Sexual Assault Prevention: College Students as Prosocial Bystanders

    ERIC Educational Resources Information Center

    Exner, Deinera; Cummings, Nina

    2011-01-01

    Prosocial bystander interventions are promising approaches to sexual assault prevention on college campuses. Objective: To assess bystander attitudes among undergraduate students at a northeastern university. Participants: A convenience sample of 188 students from 4 undergraduate classes was surveyed during regularly scheduled class sessions.…

  17. Rape Myth Beliefs and Bystander Attitudes among Incoming College Students

    ERIC Educational Resources Information Center

    McMahon, Sarah

    2010-01-01

    Objective: The bystander approach to rape prevention is gaining popularity on college campuses, although research is limited. This study explored bystander attitudes and their relationship with rape myths in a sample of college students. Participants: Surveys from 2,338 incoming undergraduate students at a large, northeastern university were…

  18. Mechanistic and quantitative studies of bystander response in 3D tissues for low-dose radiation risk estimations

    SciTech Connect

    Amundson, Sally A.

    2013-06-12

    We have used the MatTek 3-dimensional human skin model to study the gene expression response of a 3D model to low and high dose low LET radiation, and to study the radiation bystander effect as a function of distance from the site of irradiation with either alpha particles or low LET protons. We have found response pathways that appear to be specific for low dose exposures, that could not have been predicted from high dose studies. We also report the time and distance dependent expression of a large number of genes in bystander tissue. the bystander response in 3D tissues showed many similarities to that described previously in 2D cultured cells, but also showed some differences.

  19. Active Defending and Passive Bystanding Behavior in Bullying: The Role of Personal Characteristics and Perceived Peer Pressure

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca

    2010-01-01

    This study examined the role of pro-victim attitudes, personal responsibility, coping responses to observations of bullying, and perceived peer normative pressure in explaining defending the victim and passive bystanding behavior in bullying. A total of 462 Italian early adolescents (mean age = 13.4 years, SD = 9 months) participated in the study.…

  20. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness

    PubMed Central

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed. PMID:26230523

  1. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness.

    PubMed

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed. PMID:26230523

  2. Commitment and the responsive bystander: a field evaluation with a less problematic request.

    PubMed

    Guéguen, Nicolas

    2014-10-01

    Prior research on the effect of commitment on bystander intervention has focused on situations involving crime (e.g., robbery). However, the effect of commitment on less problematic situations has never been examined. In this field study, a female confederate asked (commitment condition) or did not ask (no-commitment condition) a customer to keep an eye on her grocery cart on the pretext that she had forgotten something in the store. Several seconds later, a male confederate arrived behind the first confederate's cart and began to move it in order to take her place. It was found that participants (N = 40) intervened to stop the second confederate more frequently in the commitment condition. The results support the assumption that bystander commitment influences behavior even in a non-crime situation. PMID:25153842

  3. Bystander signalling: exploring clinical relevance through new approaches and new models.

    PubMed

    Butterworth, K T; McMahon, S J; Hounsell, A R; O'Sullivan, J M; Prise, K M

    2013-10-01

    Classical radiation biology research has centred on nuclear DNA as the main target of radiation-induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly showing radiation-induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation-induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology and highlighted an important role for cells not directly traversed by radiation. The multiplicity of experimental systems and exposure conditions in which RIBEs have been observed has hindered precise definitions of these effects. However, RIBEs have recently been classified for different relevant human radiation exposure scenarios in an attempt to clarify their role in vivo. Despite significant research efforts in this area, there is little direct evidence for their role in clinically relevant exposure scenarios. In this review, we explore the clinical relevance of RIBEs from classical experimental approaches through to novel models that have been used to further determine their potential implications in the clinic. PMID:23849503

  4. Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications

    NASA Astrophysics Data System (ADS)

    Voss, K. O.; Fournier, C.; Taucher-Scholz, G.

    2008-07-01

    The risk assessment for low doses of high linear energy transfer (LET) radiation has been challenged by a growing body of experimental evidence showing that non-irradiated bystander cells can receive signals from irradiated cells to elicit a variety of cellular responses. These may be significant for radiation protection but also for radiation therapy using heavy ions. Charged particle microbeams for radiobiological application provide a unique means to address these issues by allowing the precise irradiation of single cells with a counted numbers of ions. Here, we focus specifically on heavy ion microbeam facilities currently in use for biological purposes, describing their technical features and biological results. Typically, ion species up to argon are used for targeted biological irradiation at the vertically collimated microbeam at JAEA (Takasaki, Japan). At the SNAKE microprobe in Munich, mostly oxygen ions have been used in a horizontal focused beam line for cell targeting. At GSI (Darmstadt), a horizontal microprobe with a focused beam for defined targeting using ion species up to uranium is operational. The visualization of DNA damage response proteins relocalizing to defined sites of ion traversal has been accomplished at the three heavy ion microbeam facilities described above and is used to study mechanistic aspects of heavy ion effects. However, bystander studies have constituted the main focus of biological applications. While for cell inactivation and effects on cell cycle progression a response of non-targeted cells has been described at JAEA and GSI, respectively, in part controversial results have been obtained for the induction of DNA damage measured by double-strand formation or at the cytogenetic level. The results emphasize the influence of the cellular environment, and standardization of experimental conditions for cellular studies at different facilities as well as the investigation of bystander effects in tissue will be the aims of future

  5. Standing Up for the Victim, Siding with the Bully or Standing By? Bystander Responses in Bullying Situations

    ERIC Educational Resources Information Center

    Poyhonen, Virpi; Juvonen, Jaana; Salmivalli, Christina

    2012-01-01

    In this study we examined children's self-efficacy, outcome expectations, and outcome values in relation to bystander responses in bullying situations. We proposed that beyond the effect of self-efficacy, the decision to defend the victim of bullying vs. remain passive vs. reinforce the bully depends on outcomes children expect from defending, and…

  6. Identification of Key Proteins in Human Epithelial Cells Responding to Bystander Signals From Irradiated Trout Skin

    PubMed Central

    Smith, Richard; Wang, Jiaxi; Seymour, Colin; Mothersill, Carmel; Howe, Orla

    2015-01-01

    Radiation-induced bystander signaling has been found to occur in live rainbow trout fish (Oncorhynchus mykiss). This article reports identification of key proteomic changes in a bystander reporter cell line (HaCaT) grown in low-dose irradiated tissue-conditioned media (ITCM) from rainbow trout fish. In vitro explant cultures were generated from the skin of fish previously exposed to low doses (0.1 and 0.5 Gy) of X-ray radiation in vivo. The ITCM was harvested from all donor explant cultures and placed on recipient HaCaT cells to observe any change in protein expression caused by the bystander signals. Proteomic methods using 2-dimensional (2D) gel electrophoresis and mass spectroscopy were employed to screen for novel proteins expressed. The proteomic changes measured in HaCaT cells receiving the ITCM revealed that exposure to 0.5 Gy induced an upregulation of annexin A2 and cingulin and a downregulation of Rho-GDI2, F-actin-capping protein subunit beta, microtubule-associated protein RP/EB family member, and 14-3-3 proteins. The 0.1 Gy dose also induced a downregulation of Rho-GDI2, hMMS19, F-actin-capping protein subunit beta, and microtubule-associated protein RP/EB family member proteins. The proteins reported may influence apoptotic signaling, as the results were suggestive of an induction of cell communication, repair mechanisms, and dysregulation of growth signals. PMID:26673684

  7. Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses

    SciTech Connect

    Kevin M. Prise

    2007-01-02

    The overall goal is characterization of 3D tissue models that can be used for investigation of the mechanisms underlying radiation-induced bystander effect at low doses (20 cGy or less) of low LET ionizing radiation, using a unique focused soft X-ray microprobe that had been upgraded to provide a range of focused soft X-ray energies, some sufficient to penetrate 3D models (Ref DE-FG02-01ER63236). The proposed studies will include an examination of whether the passage of a single electron track can trigger bystander responses in the 3D tissue models and, if so, whether the response is altered by increased or decreased levels of oxidative stress. Our existing multi-photon/confocal in-depth microscopy techniques will be used to develop assays for damage induced within intact 3D tissue models. The working hypothesis is that organization of cells into tissues, particularly involving more than one cell type, alters expression of the radiation-induced bystander effect compared to that seen in isolated single cell types in monolayer.

  8. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    SciTech Connect

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  9. Observational Learning and the Effects of Model-Observer Similarity.

    ERIC Educational Resources Information Center

    Braaksma, Martine A. H.; Rijlaarsdam, Gert; van den Bergh, Huub

    2002-01-01

    This study examined the effects of similarity in competence between model and observer on the effectiveness of observational learning in argumentative writing. Results are consistent with the similarity hypothesis: weak learners learn more from focusing their observations on weak models, whereas better learners learn more from focusing on good…

  10. Gender differences in attitudes and beliefs associated with bystander behavior and sexual assault.

    PubMed

    Amar, Angela F; Sutherland, Melissa; Laughon, Kathryn

    2014-01-01

    Sexual violence is a significant problem on many college campuses. Bystander education programs have been found to train individuals to act to prevent sexual and partner violence and improve the responses of peers to survivors. Limited evidence suggests that gender differences exist between males and females regarding both attitudes toward, and use of, bystander behavior, with females reporting more supportive attitudes and greater use of bystander behavior. The purpose of this study is to compare male and female college students on attitudes toward date rape, bystander efficacy, intention to act as a bystander, and actual use of bystander behaviors. A secondary aim explored gender differences in theoretically driven bystander behaviors and barriers to acting as a bystander. A convenience sample of 157 full-time undergraduate students aged 18-24 years completed survey measures of attitudes related to sexual and partner violence and willingness to help. Analysis of variance and chi-square were used to compare gender differences in scores. Significant gender differences were found for date rape attitudes, efficacy, and intention to act as a positive bystander. Men reported more rape-supportive attitudes and greater intention to act as a bystander than women, whereas women reported greater levels of bystander efficacy than men. The findings can be used in tailoring gender-specific components of bystander education programs for sexual assault prevention and intervention. PMID:24762431

  11. A Randomized Controlled Trial of a Multi-Dose Bystander Intervention Program Using Peer Education Theater

    ERIC Educational Resources Information Center

    McMahon, Sarah; Winter, Samantha C.; Palmer, Jane E.; Postmus, Judy L.; Peterson, N. Andrew; Zucker, Sharon; Koenick, RuthAnne

    2015-01-01

    This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend…

  12. [Potential laser hazards to bystanders during photocoagulation].

    PubMed

    Okamoto, N; Harino, S; Saito, Y; Ogawa, K

    1993-02-01

    The authors measured reflected laser beams delivered by slit-lamp photocoagulator and binocular indirect ophthalmoscope laser delivery systems, to evaluate potential hazards to the eyes of bystanders. 514 nm laser beams were used; reflected laser beams were measured by a light power meter (Advantest: TQ8210). Reflected lasers were found to be hazardous at 1 meter from whitish tile when a 0.75 Watt laser beam was delivered by the binocular ophthalmoscope laser system, as in an operating room. At 1 meter from a wall in a photo-coagulating room for out-patients, the reflected laser beam was found to be well below hazardous levels. Reflections at 40 cm from a non-laser-coated Goldmann 3-mirror contact lens were 2.66 mW/cm2, which exceeds the exposure limits, when 0.3 W laser was delivered by the slit-lamp photocoagulator. This decreased 85-90% when the laser was reflected from a laser-coated lens. From the point of view of safety, it is recommended that laser surgeons replace non-laser-coated lenses with laser-coated ones. PMID:8475831

  13. Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering

    PubMed Central

    2011-01-01

    Background The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation, but the signaling mechanisms between irradiated and non-irradiated bystander cells are not fully understood. In this study, we measured a time-series of gene expression after α-particle irradiation and applied the Feature Based Partitioning around medoids Algorithm (FBPA), a new clustering method suitable for sparse time series, to identify signaling modules that act in concert in the response to direct irradiation and bystander signaling. We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM). Results While computational evaluations of both clustering results were similar, FBPA provided more biological insight. After irradiation, gene clusters were enriched for signal transduction, cell cycle/cell death and inflammation/immunity processes; but only FBPA separated clusters by function. In bystanders, gene clusters were enriched for cell communication/motility, signal transduction and inflammation processes; but biological functions did not separate as clearly with either clustering method as they did in irradiated samples. Network analysis confirmed p53 and NF-κB transcription factor-regulated gene clusters in irradiated and bystander cells and suggested novel regulators, such as KDM5B/JARID1B (lysine (K)-specific demethylase 5B) and HDACs (histone deacetylases), which could epigenetically coordinate gene expression after irradiation. Conclusions In this study, we have shown that a new time series clustering method, FBPA, can provide new leads to the mechanisms regulating the dynamic cellular response to radiation. The findings implicate epigenetic control of gene expression in addition to transcription factor networks. PMID:21205307

  14. microRNAome changes in bystander three-dimensional human tissue models suggest priming of apoptotic pathways

    PubMed Central

    Kovalchuk, Olga; Zemp, Franz J.; Filkowski, Jody N.; Altamirano, Alvin M.; Dickey, Jennifer S.; Jenkins-Baker, Gloria; Marino, Stephen A.; Brenner, David J.; Bonner, William M.; Sedelnikova, Olga A.

    2010-01-01

    The radiation-induced bystander effect (RIBE) is a phenomenon whereby unexposed cells exhibit molecular symptoms of stress exposure when adjacent or nearby cells are traversed by ionizing radiation (IR). Recent data suggest that RIBE may be epigenetically mediated by microRNAs (miRNAs), which are small regulatory molecules that target messenger RNA transcripts for translational inhibition. Here, we analyzed microRNAome changes in bystander tissues after α-particle microbeam irradiation of three-dimensional artificial human tissues using miRNA microarrays. Our results indicate that IR leads to a deregulation of miRNA expression in bystander tissues. We report that major bystander end points, including apoptosis, cell cycle deregulation and DNA hypomethylation, may be mediated by altered expression of miRNAs. Specifically, c-MYC-mediated upregulation of the miR-17 family was associated with decreased levels of E2F1 and RB1, suggesting a switch to a proliferative state in bystander tissues, while priming these cells for impending death signals. Upregulation of the miR-29 family resulted in decreased levels of its targets DNMT3a and MCL1, consequently affecting DNA methylation and apoptosis. Altered expression of miR-16 led to changes in expression of BCL2, suggesting modulation of apoptosis. Thus, our data clearly show that miRNAs play a profound role in the manifestation of late RIBE end points. In summary, this study creates a roadmap for understanding the role of microRNAome in RIBE and for developing novel RIBE biomarkers. PMID:20643754

  15. Why are bystanders friendly to recipients of aggression?

    PubMed Central

    Koski, Sonja E; Wittig, Roman M; Aureli, Filippo

    2009-01-01

    The escalation of conflicts of interest into aggressive conflict can be costly in terms of increased post-conflict stress and damage to the opponents' relationship. Some costs may be mitigated through post-conflict interactions. One such type of interaction is affiliative contact from a bystander to the recipient of aggression. This type of interaction has been suggested to have a number of functions, including stress reduction and opponent relationship repair. It may also protect bystanders from redirected aggression from the original recipient of aggression. Here we review the evidence for such functions and propose a framework within which the function and occurrence of post-conflict affiliation directed from a bystander to the recipient of aggression is related to the quality of the relationships between the individuals involved and the patterns of behavior expressed. PMID:19641753

  16. Why are bystanders friendly to recipients of aggression?

    PubMed

    Fraser, Orlaith N; Koski, Sonja E; Wittig, Roman M; Aureli, Filippo

    2009-05-01

    The escalation of conflicts of interest into aggressive conflict can be costly in terms of increased post-conflict stress and damage to the opponents' relationship. Some costs may be mitigated through post-conflict interactions. One such type of interaction is affiliative contact from a bystander to the recipient of aggression. This type of interaction has been suggested to have a number of functions, including stress reduction and opponent relationship repair. It may also protect bystanders from redirected aggression from the original recipient of aggression. Here we review the evidence for such functions and propose a framework within which the function and occurrence of post-conflict affiliation directed from a bystander to the recipient of aggression is related to the quality of the relationships between the individuals involved and the patterns of behavior expressed. PMID:19641753

  17. The Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis Offers Efficient Bystander Cell Killing for Suicide Gene Therapy of Cancer

    PubMed Central

    Lavie, Arnon; Yanagisawa, Teruyuki; Medin, Jeffrey A.

    2013-01-01

    We previously described a novel suicide (or ‘cell fate control’) gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo. Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs). Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression – an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43) and Pannexin1 (Panx1), but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs. PMID:24194950

  18. The engineered thymidylate kinase (TMPK)/AZT enzyme-prodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer.

    PubMed

    Sato, Takeya; Neschadim, Anton; Lavie, Arnon; Yanagisawa, Teruyuki; Medin, Jeffrey A

    2013-01-01

    We previously described a novel suicide (or 'cell fate control') gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo. Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs). Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression--an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43) and Pannexin1 (Panx1), but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs. PMID:24194950

  19. Mechanism of bystander-blaming: defensive attribution, counterfactual thinking, and gender.

    PubMed

    Levy, Inna; Ben-David, Sarah

    2015-01-01

    Contemporary victimology recognizes that an understanding of the mechanism of blaming requires a comprehensive approach that includes the victim, the offender, and the bystander. However, most of the existing research on blaming focuses on the victim and the offender, ignoring the issue of bystander-blaming. This study highlights the bystander and investigates bystander-blaming by exploring some theoretical explanations, including counterfactual thinking, defensive attribution, and gender differences. The study included 363 young male and female participants, who read vignettes describing the behavior of the victim and the bystander in a rape scenario and answered questions regarding bystander-blaming. The results show that both counterfactual thinking and defensive attribution play a role in bystander-blaming. This article addresses the theoretical and practical implications of these findings. PMID:24052599

  20. Bullying victimization and the social and emotional maladjustment of bystanders: A propensity score analysis.

    PubMed

    Werth, Jilynn M; Nickerson, Amanda B; Aloe, Ariel M; Swearer, Susan M

    2015-08-01

    This study investigated how bystanders, who have and have not been bullied, perceive their social and emotional maladjustment depending on the form of bullying (physical or verbal) they witness. Using propensity score matching, equivalent groups of 270 victimized and 270 non-victimized bystander groups were created based on middle school students' responses on the Bully Survey-Student Version (BYS-S; Swearer, 2001). Victimized bystanders experienced higher social maladjustment than non-victimized bystanders. Path analysis results suggest that social and emotional maladjustment as a bystander is related not only to social-emotional maladjustment as victim, but to gender and the form of bullying witnessed. The way in which bystanders are influenced by their personal victimization may be a critical factor in predicting, understanding, and increasing active bystander intervention. PMID:26270274

  1. Unique aspects of mda-7/IL-24 antitumor bystander activity: establishing a role for secretion of MDA-7/IL-24 protein by normal cells.

    PubMed

    Su, Zhaozhong; Emdad, Luni; Sauane, Moira; Lebedeva, Irina V; Sarkar, Devanand; Gupta, Pankaj; James, C David; Randolph, Aaron; Valerie, Kirstoffer; Walter, Mark R; Dent, Paul; Fisher, Paul B

    2005-11-17

    Melanoma differentiation associated gene-7 (mda-7) was cloned using subtraction hybridization from terminally differentiated human melanoma cells. Based on structural and functional properties, mda-7 is now recognized as interleukin-24 (IL-24), a new member of the expanding IL-10 gene family. Unique properties of mda-7/IL-24 include its ability to selectively induce growth suppression, apoptosis and radiosensitization in diverse human cancer cells, without causing similar effects in normal cells. The utility of mda-7/IL-24, administered by means of a replication-incompetent adenovirus, as a gene therapy for cancer has recently received validation in patients, highlighting an important phenomenon initially observed in pancreatic tumor cells, namely a 'potent bystander apoptosis-inducing effect' in adjacent tumor cells not initially receiving this gene product. We presently investigated the contribution of mda-7/IL-24 secreted by normal cells in mediating this 'bystander effect', and document that normal cells induced to produce mda-7/IL-24 following infection with recombinant adenoviruses expressing this cytokine secrete mda-7/IL-24, which modifies the anchorage-independent growth, invasiveness, survival and sensitivity to radiation of cancer cells that contain functional IL-20/IL-22 receptors, but not in cancer cells that lack a complete set of receptors. Moreover, the combination of secreted mda-7/IL-24 and radiation engenders a 'bystander antitumor effect' not only in inherently mda-7/IL-24 or radiation-sensitive cancer cells, but also in tumor cells overexpressing the antiapoptotic proteins bcl-2 or bcl-x(L) and displaying resistance to either treatment alone. The present studies provide definitive evidence that secreted mda-7/IL-24 from normal cells can induce direct antitumor and radiation-enhancing effects that are dependent on the presence of canonical receptors for this cytokine on tumor cells. Moreover, we now describe a novel means of enhancing mda-7/IL

  2. Irradiated human endothelial progenitor cells induce bystander killing in human non-small cell lung and pancreatic cancer cells.

    PubMed

    Turchan, William T; Shapiro, Ronald H; Sevigny, Garrett V; Chin-Sinex, Helen; Pruden, Benjamin; Mendonca, Marc S

    2016-08-01

    Purpose To investigate whether irradiated human endothelial progenitor cells (hEPC) could induce bystander killing in the A549 non-small cell lung cancer (NSCLC) cells and help explain the improved radiation-induced tumor cures observed in A549 tumor xenografts co-injected with hEPC. Materials and methods We investigated whether co-injection of CBM3 hEPC with A549 NSCLC cells would alter tumor xenograft growth rate or tumor cure after a single dose of 0 or 5 Gy of X-rays. We then utilized dual chamber Transwell dishes, to test whether medium from irradiated CBM3 and CBM4 hEPC would induce bystander cell killing in A549 cells, and as an additional control, in human pancreatic cancer MIA PaCa-2 cells. The CBM3 and CBM4 hEPC were plated into the upper Transwell chamber and the A549 or MIA PaCa-2 cells were plated in the lower Transwell chamber. The top inserts with the CBM3 or CBM4 hEPC cells were subsequently removed, irradiated, and then placed back into the Transwell dish for 3 h to allow for diffusion of any potential bystander factors from the irradiated hEPC in the upper chamber through the permeable membrane to the unirradiated cancer cells in the lower chamber. After the 3 h incubation, the cancer cells were re-plated for clonogenic survival. Results We found that co-injection of CBM3 hEPC with A549 NSCLC cells significantly increased the tumor growth rate compared to A549 cells alone, but paradoxically also increased A549 tumor cure after a single dose of 5 Gy of X-rays (p < 0.05). We hypothesized that irradiated hEPC may be inducing bystander killing in the A549 NSCLC cells in tumor xenografts, thus improving tumor cure. Bystander studies clearly showed that exposure to the medium from irradiated CBM3 and CBM4 hEPC induced significant bystander killing and decreased the surviving fraction of A549 and MIA PaCa-2 cells to 0.46 (46%) ± 0.22 and 0.74 ± 0.07 (74%) respectively (p < 0.005, p < 0.0001). In addition, antibody depletion

  3. Changing attitudes about being a bystander to violence: translating an in-person sexual violence prevention program to a new campus.

    PubMed

    Cares, Alison C; Banyard, Victoria L; Moynihan, Mary M; Williams, Linda M; Potter, Sharyn J; Stapleton, Jane G

    2015-02-01

    Bystander approaches to reducing sexual violence train community members in prosocial roles to interrupt situations with risk of sexual violence and be supportive community allies after an assault. This study employs a true experimental design to evaluate the effectiveness of Bringing in the Bystander™ through 1-year post-implementation with first-year students from two universities (one rural, primarily residential; one urban, heavily commuter). We found significant change in bystander attitudes for male and female student program participants compared with the control group on both campuses, although the pattern of change depended on the combination of gender and campus. PMID:25540255

  4. Rehearsing for real life: the impact of the InterACT Sexual Assault Prevention Program on self-reported likelihood of engaging in bystander interventions.

    PubMed

    Ahrens, Courtney E; Rich, Marc D; Ullman, Jodie B

    2011-06-01

    The interACT Sexual Assault Prevention Program is an interactive, skill-building performance based on the pedagogy of Augusto Boal's Theatre of the Oppressed. A longitudinal evaluation of this program compared pretest, posttest, and 3-month follow-up data from 509 university student participants. Results suggested that the interACT performance was successful in increasing participants' beliefs about the effectiveness of bystander interventions and the self-rated likelihood that participants would engage in bystander interventions in the future. Differences in both overall ratings and rates of change were noted. Implications of these results for research and practice are discussed. PMID:21628338

  5. Preventing sexual aggression among college men: an evaluation of a social norms and bystander intervention program.

    PubMed

    Gidycz, Christine A; Orchowski, Lindsay M; Berkowitz, Alan D

    2011-06-01

    Men and women living in randomly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs, respectively. An evaluation of the men's project is presented (N = 635). The program incorporated social norms and bystander intervention education and had an impact on self-reported sexual aggression and an effect on men's perceptions that their peers would intervene when they encountered inappropriate behavior in others. Relative to the control group, participants also reported less reinforcement for engaging in sexually aggressive behavior, reported fewer associations with sexually aggressive peers, and indicated less exposure to sexually explicit media. PMID:21571742

  6. A Qualitative Exploration of Cyber-Bystanders and Moral Engagement

    ERIC Educational Resources Information Center

    Price, Deborah; Green, Deborah; Spears, Barbara; Scrimgeour, Margaret; Barnes, Alan; Geer, Ruth; Johnson, Bruce

    2014-01-01

    Studies have found that moral disengagement plays a significant role in the continuation of bullying situations (Bonanno, 2005); however, the moral stance of cyber-bystanders--those who witness online bullying--is not yet clear. While research into traditional face-to-face bullying reported that peers would probably or certainly intervene to…

  7. Incoming College Students' Bystander Behaviors to Prevent Sexual Violence

    ERIC Educational Resources Information Center

    McMahon, Sarah; Banyard, Victoria L.; McMahon, Sheila M.

    2015-01-01

    Evaluations of bystander intervention education programs demonstrate that this approach results in students' increased willingness to intervene in prosocial ways to prevent sexual violence (e.g., Moynihan, Banyard, Arnold, Eckstein, & Stapleton, 2010). These programs often focus on first-year college students, though theories and research on…

  8. Bystander Reaction to Women Fighting: Developing a Theory of Intervention

    ERIC Educational Resources Information Center

    Lowe, Robert D.; Levine, Mark; Best, Rachel M.; Heim, Derek

    2012-01-01

    This article explores accounts of bystanders to female-on-female public violence. Group interviews with participants in the night-time economy are carried out. Whereas men tend to respond to the discussion topic of female-on-female violence with laughter, this laughter reveals ambivalence and discomfort as much as amusement. Men seem to negotiate…

  9. AutoTutor Passes the Bystander Turing Test.

    ERIC Educational Resources Information Center

    Person, Natalie; Erkel, Mary; Graesser, Arthur C.

    In this study, the Bystander Turing Test (BTT) paradigm is used to determine whether participants rate particular dialog moves in tutoring transcripts to be generated by a computer tutor, AutoTutor, or by a skilled human tutor. Currently, AutoTutor initiates a conversation with the learner by posing a question or presenting a problem for the…

  10. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells.

    PubMed

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin

    2016-07-01

    Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. PMID:27155559

  11. Active defending and passive bystanding behavior in bullying: the role of personal characteristics and perceived peer pressure.

    PubMed

    Pozzoli, Tiziana; Gini, Gianluca

    2010-08-01

    This study examined the role of pro-victim attitudes, personal responsibility, coping responses to observations of bullying, and perceived peer normative pressure in explaining defending the victim and passive bystanding behavior in bullying. A total of 462 Italian early adolescents (mean age = 13.4 years, SD = 9 months) participated in the study. The behaviors were measured through two informants: each individual student and the teachers. The findings of a series of hierarchical regressions showed that, regardless of the informant, problem solving coping strategies and perceived peer normative pressure for intervention were positively associated with active help towards a bullied peer and negatively related to passivity. In contrast, distancing strategies were positively associated with passive bystanding, whereas they were negatively associated with teacher-reported defending behavior. Moreover, self-reported defending behavior was positively associated with personal responsibility for intervention, but only under conditions of low perceived peer pressure. Finally, the perception of peer pressure for intervention buffered the negative influence of distancing on passive bystanding tendencies. Future directions are discussed. PMID:20228996

  12. Workplace mobbing and bystanders' helping behaviour towards victims: the role of gender, perceived responsibility and anticipated stigma by association.

    PubMed

    Mulder, Roelie; Pouwelse, Mieneke; Lodewijkx, Hein; Bolman, Catherine

    2014-08-01

    We examined victims' perceived responsibility and bystanders' anticipated risk of being victimized themselves when others associate them with the victim (stigma by association, SBA) as possible antecedents of bystanders' helping behaviour towards a victim of workplace mobbing, and explored the effects of gender. Guided by the attribution model of social conduct (Weiner, 2006), a 2 × 2 vignette experiment was conducted. Participants were Dutch regional government employees (N = 161). Path analyses generally supported the hypotheses, but showed different results for women and men. In the strong (Vs. weak) responsibility condition, women reported less sympathy and more anger and men only more anger, which resulted in lower helping intention. Additionally, for men the results showed an unexpected direct positive effect of responsibility on helping intention. Furthermore, in the strong SBA condition, women and men reported more fear and men, unexpectedly, more anger. Consequently, helping intention decreased. The findings on gender are discussed in the context of social role theory, gender and emotion. Our findings suggest that to prevent and tackle mobbing, organizations and professionals should be aware of the attributional and emotional processes and gender differences in bystanders' helping behaviour. PMID:24990642

  13. Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.

    PubMed

    White, Jason T; Cross, Eric W; Burchill, Matthew A; Danhorn, Thomas; McCarter, Martin D; Rosen, Hugo R; O'Connor, Brian; Kedl, Ross M

    2016-01-01

    Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity. PMID:27097762

  14. Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner

    PubMed Central

    White, Jason T.; Cross, Eric W.; Burchill, Matthew A.; Danhorn, Thomas; McCarter, Martin D.; Rosen, Hugo R.; O'Connor, Brian; Kedl, Ross M.

    2016-01-01

    Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity. PMID:27097762

  15. Electronic cigarettes and indoor air quality: a simple approach to modeling potential bystander exposures to nicotine.

    PubMed

    Colard, Stéphane; O'Connell, Grant; Verron, Thomas; Cahours, Xavier; Pritchard, John D

    2015-01-01

    There has been rapid growth in the use of electronic cigarettes ("vaping") in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents. PMID:25547398

  16. Electronic Cigarettes and Indoor Air Quality: A Simple Approach to Modeling Potential Bystander Exposures to Nicotine

    PubMed Central

    Colard, Stéphane; O’Connell, Grant; Verron, Thomas; Cahours, Xavier; Pritchard, John D.

    2014-01-01

    There has been rapid growth in the use of electronic cigarettes (“vaping”) in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents. PMID:25547398

  17. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells.

    PubMed

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  18. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells

    PubMed Central

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  19. Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity

    PubMed Central

    Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Alsahafi, Nirmin; Coutu, Mathieu; Brassard, Nathalie; Park, Jongwoo; Courter, Joel R.; Melillo, Bruno; Smith, Amos B.; Shaw, George M.; Hahn, Beatrice H.; Sodroski, Joseph; Kaufmann, Daniel E.; Finzi, Andrés

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells. PMID:26870823

  20. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses.

    PubMed

    Tomita, Masanori; Maeda, Munetoshi

    2015-03-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

  1. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

    PubMed Central

    Tomita, Masanori; Maeda, Munetoshi

    2015-01-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

  2. Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

    PubMed

    Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

    2015-11-01

    The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge. PMID:25995267

  3. Conceptualizing the Engaging Bystander Approach to Sexual Violence Prevention on College Campuses

    ERIC Educational Resources Information Center

    McMahon, Sarah; Postmus, Judy L.; Koenick, Ruth Anne

    2011-01-01

    Bystander intervention offers promise as a sexual violence prevention tool for student affairs administrators on college campuses, but the conceptualization and definition of the approach is in its infancy and needs further development. In an effort to emphasize the potential role of bystanders in the primary prevention of sexual violence, we put…

  4. Why Do Bystanders of Bullying Help or Not? A Multidimensional Model

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca

    2013-01-01

    The authors employed Latane and Darley's model about bystanders' behavior to explain children's active defending and passive bystanding behavior in school bullying. The three central steps of the model were operationalized by measuring provictim attitudes, personal responsibility for intervention, and coping strategies. Moreover,…

  5. Contributions of Personal and Situational Factors to Bystanders' Reactions to School Bullying

    ERIC Educational Resources Information Center

    Oh, Insoo; Hazler, Richard J.

    2009-01-01

    The intent of this study was to explore bystanders' personal and situational variables predicting their behavioural reactions to school bullying by investigating a sample of 298 college students who had witnessed bullying during middle or high school. Results indicated that the bystander personal variables, gender and past experience as a bully or…

  6. Roles of Fatalism and Parental Support in the Relationship between Bullying Victimization and Bystander Behaviors

    ERIC Educational Resources Information Center

    Li, Yiqiong; Chen, Peter Y.; Chen, Fu-Li; Wu, Wen-Chi

    2015-01-01

    This article examines how past bullied victims engage two types of bystander behaviors (defender and outsider) when they witness bullying situations.We also investigate if fatalism mediates the relationship between past victimization and two bystander behaviors. Finally, we test if parental support moderates the relationship between fatalism and…

  7. Individual Motivations and Characteristics Associated with Bystander Intervention during Bullying Episodes among Children and Youth

    ERIC Educational Resources Information Center

    Cappadocia, M. Catherine; Pepler, Debra; Cummings, Joanne G.; Craig, Wendy

    2012-01-01

    The aim of the current study was to explore bystander experiences during bullying episodes among children and youth attending a residential summer camp by investigating rates of witnessing and intervention, as well as individual motivations and characteristics associated with bystander intervention. The majority of children had witnessed bullying…

  8. What Would You Do? Strategies for Bystander Intervention to Prevent Sexual Violence by College Students

    ERIC Educational Resources Information Center

    McMahon, Sarah; Hoffman, Melanie Lowe; McMahon, Sheila M.; Zucker, Sharon; Koenick, Ruth Anne

    2013-01-01

    Bystander education is an increasingly utilized strategy for addressing sexual assault prevention and intervention on U.S. college campuses. Given the paramount importance of peers among college students, what types of pro-social bystander interventions do students themselves deem feasible in the campus context? Drawing on self-reports from…

  9. On Standby? A Comparison of Online and Offline Witnesses to Bullying and Their Bystander Behaviour

    ERIC Educational Resources Information Center

    Quirk, Roslynn; Campbell, Marilyn

    2015-01-01

    Given their ubiquitous presence as witnesses to school-yard bullying, the role of the "bystander" has been studied extensively. The prevalence and behaviour of bystanders to "cyberbullying," however, is less understood. In an anonymous, school-based questionnaire, 716 secondary school students from South-East Queensland…

  10. Observations and Effects of Dipolarization Fronts Observed in Earth's Magnetotail

    NASA Technical Reports Server (NTRS)

    Goldstein, Melvyn L.

    2011-01-01

    Dipolarization fronts in Earth's magnetotail are characterized by sharp jumps in magnetic field, a drop in density, and often follow earthward fast plasma flow. They are commonly detected near the equatorial plane of Earth s tail plasma sheet. Sometimes, but not always, dipolarization fronts are associated with global substorms and auroral brightenings. Both Cluster, THEMIS, and other spacecraft have detected dipolarization fronts in a variety of locations in the magnetotail. Using multi-spacecraft analyses together with simulations, we have investigated the propagation and evolution of some dipolarization events. We have also investigated the acceleration of electrons and ions that results from such magnetic-field changes. In some situations, the velocities of fast earthward flows are comparable to the Alfven speed, indicating that the flow bursts might have been generated by bursty reconnection that occurred tailward of the spacecraft. Based on multi-spacecraft timing analysis, dipolarization fronts are found to propagate mainly earthward at 160-335 km/s and have thicknesses of 900-1500 km, which corresponds to the ion inertial length or gyroradius scale. Following the passage of dipolarization fronts, significant fluctuations are observed in the x and y components of the magnetic field. These peaks in the magnetic field come approximately 1-2 minutes after passage of the dipolarization front. These Bx and By fluctuations propagate primarily dawnward and earthward. Field-aligned electron beams are observed coincident with those magnetic field fluctuations. Non-Maxwellian electron and ion distributions are observed that are associated with the dipolarization that may be unstable to a range of electrostatic and/or whistler instabilities. Enhanced electrostatic broadband noise at frequencies below and near the lower-hybrid frequency is also observed at or very close to these fronts. This broadband noise is thought to play a role in further energizing the particles

  11. Adolescent bystanders' perspectives of aggression in the online versus school environments.

    PubMed

    Patterson, Lisa J; Allan, Alfred; Cross, Donna

    2016-06-01

    Researchers' understanding of bystanders' perspectives in the cyber-environment fails to take young people's perceptions into account and remains imperfect. Interventions encouraging adolescents to help targets of cyber-aggression are therefore typically based upon traditional school-based aggression research. Twenty-four in-depth interviews with Australian 13-16 year-olds revealed two themes that reflect how young bystanders perceive differences between aggression online and at school. The physical presence theme suggests that young bystanders struggle to determine online intentions in the absence of body language, leading to hesitancy in reactions and furthermore make it easier for them to ignore online transgressions and avoid becoming involved. The authority theme indicates young bystanders perceive that, compared to the school environment, the online environment lacks clearly established rules, authority figures and formal reporting mechanisms. These differences indicate that unique strategies should be developed to encourage young bystanders to intervene in cyber-aggression situations. PMID:27007497

  12. Measurement of the bystander intervention model for bullying and sexual harassment.

    PubMed

    Nickerson, Amanda B; Aloe, Ariel M; Livingston, Jennifer A; Feeley, Thomas Hugh

    2014-06-01

    Although peer bystanders can exacerbate or prevent bullying and sexual harassment, research has been hindered by the absence of a validated assessment tool to measure the process and sequential steps of the bystander intervention model. A measure was developed based on the five steps of Latané and Darley's (1970) bystander intervention model applied to bullying and sexual harassment. Confirmatory factor analysis with a sample of 562 secondary school students confirmed the five-factor structure of the measure. Structural equation modeling revealed that all the steps were influenced by the previous step in the model, as the theory proposed. In addition, the bystander intervention measure was positively correlated with empathy, attitudes toward bullying and sexual harassment, and awareness of bullying and sexual harassment facts. This measure can be used for future research and to inform intervention efforts related to the process of bystander intervention for bullying and sexual harassment. PMID:24793386

  13. Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

    PubMed

    Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

    2016-07-01

    Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

  14. A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled Trial

    PubMed Central

    Vivolo-Kantor, Alana; Hardin, James; Berkowitz, Alan

    2014-01-01

    Background Bystander intervention approaches offer promise for reducing rates of sexual violence on college campuses. Most interventions are in-person small-group formats, which limit their reach and reduce their overall public health impact. Objective This study evaluated the efficacy of RealConsent, a Web-based bystander approach to sexual violence prevention, in enhancing prosocial intervening behaviors and preventing sexual violence perpetration. Methods A random probability sample of 743 male undergraduate students (aged 18 to 24 years) attending a large, urban university located in the southeastern United States was recruited online and randomized to either RealConsent (n=376) or a Web-based general health promotion program (n=367). Participants were surveyed online at baseline, postintervention, and 6-months postintervention. RealConsent was delivered via a password-protected Web portal that contained six 30-minute media-based and interactive modules covering knowledge of informed consent, communication skills regarding sex, the role of alcohol and male socialization in sexual violence, empathy for rape victims, and bystander education. Primary outcomes were self-reported prosocial intervening behaviors and sexual violence perpetration. Secondary outcomes were theoretical mediators (eg, knowledge, attitudes). Results At 6-month follow-up RealConsent participants intervened more often (P=.04) and engaged in less sexual violence perpetration (P=.04) compared to controls. In addition, RealConsent participants reported greater legal knowledge of sexual assault (P<.001), greater knowledge of effective consent (P<.001), less rape myths (P<.001), greater empathy for rape victims (P<.001), less negative date rape attitudes (P<.001), less hostility toward women (P=.01), greater intentions to intervene (P=.04), less hyper-gender ideology (P<.001), less positive outcome expectancies for nonconsensual sex (P=.03), more positive outcome expectancies for intervening (P

  15. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors.

    PubMed

    Sharma, Neha; Colangelo, Nicholas W; de Toledo, Sonia M; Azzam, Edouard I

    2016-08-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or (137)Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < .001), activation of c-jun N-terminal kinase, and decrease in the active form of FoxO3a. The induced oxidative stress was associated with phosphorylation of p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin dependent kinase inhibitors p21(Waf1) and p27(Kip1), and perturbations in cell cycle progression (p < .001). These changes were also associated with increased apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8 activation (p < .05) and altered expression of critical regulators of self-renewal, proliferation, and differentiation. Exposure of the tumor cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells. PMID:27511909

  16. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

    PubMed Central

    Sharma, Neha; Colangelo, Nicholas W.; de Toledo, Sonia M.

    2016-01-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or 137Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < .001), activation of c-jun N-terminal kinase, and decrease in the active form of FoxO3a. The induced oxidative stress was associated with phosphorylation of p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin dependent kinase inhibitors p21Waf1 and p27Kip1, and perturbations in cell cycle progression (p < .001). These changes were also associated with increased apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8 activation (p < .05) and altered expression of critical regulators of self-renewal, proliferation, and differentiation. Exposure of the tumor cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells. PMID:27511909

  17. Exercise-related sudden cardiac arrest in London: incidence, survival and bystander response

    PubMed Central

    Edwards, Melanie J; Fothergill, Rachael T

    2015-01-01

    Objective The study aimed to (1) establish the incidence of exercise-related sudden cardiac arrest (SCA) in London, (2) investigate survival from exercise-related SCA and (3) examine factors related to survival. Method This retrospective observational study examined 2 years’ data from the London Ambulance Service (LAS) cardiac arrest registry for patients in whom resuscitation was attempted following an out-of-hospital cardiac arrest (OHCA), a cardiac cause was presumed and the arrest occurred during or within 1 h of exercise. Results The incidence of exercise-related SCA in London was estimated to be 0.6 per 100 000 person-years which equated to 0.5% of all OHCA, and 1.5% of all OHCA with presumed cardiac aetiology and resuscitation attempted. The majority of cases were male and the incidence increased from age 40 years. Just under one-third of patients survived to hospital discharge. Survival in the Utstein comparator group (cases with presumed cardiac aetiology, resuscitation attempted, bystander witnessed and a presenting cardiac rhythm of ventricular fibrillation or tachycardia) was higher at 42%. Survival was significantly associated with initial cardiac rhythm (χ2=17.5, df=2, p<0.001) and bystander defibrillation (Fisher's exact test, p<0.05). Conclusions Incidence of exercise-related SCA in the general population in London is rare. Survival following exercise-related SCA was considerably higher than survival for all OHCA with presumed cardiac aetiology and resuscitation attempted attended by the LAS during the same period. The major limitation of the study is the likely under identification of cases of exercise-related SCA. PMID:26468401

  18. Observations of the Askaryan Effect in Ice

    SciTech Connect

    Gorham, P.W.

    2007-01-16

    We report on the first observations of the Askaryan effect in ice: coherent impulsive radio Cherenkov radiation from the charge asymmetry in an electromagnetic (EM) shower. Such radiation has been observed in silica sand and rock salt, but this is the first direct observation from an EM shower in ice. These measurements are important since the majority of experiments to date that rely on the effect for ultra-high energy neutrino detection are being performed using ice as the target medium. As part of the complete validation process for the Antarctic Impulsive Transient Antenna (ANITA) experiment, we performed an experiment at the Stanford Linear Accelerator Center (SLAC) in June 2006 using a 7.5 metric ton ice target, yielding results fully consistent with theoretical expectations.

  19. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students.

    PubMed

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents' risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims' and parents' educations play a more important role in peer victimization than previously thought. PMID:27472354

  20. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students

    PubMed Central

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents’ risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims’ and parents’ educations play a more important role in peer victimization than previously thought. PMID:27472354

  1. Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK.

    PubMed

    Remoundou, K; Brennan, M; Sacchettini, G; Panzone, L; Butler-Ellis, M C; Capri, E; Charistou, A; Chaideftou, E; Gerritsen-Ebben, M G; Machera, K; Spanoghe, P; Glass, R; Marchis, A; Doanngoc, K; Hart, A; Frewer, L J

    2015-02-01

    The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with passive and occupational exposure to pesticide potentially influence the extent to which different stakeholders adopt self-protective behaviour. A methodology for assessing the link between attitudes, adoption of self-protective behaviours and exposure was developed and tested. A survey was implemented in the Greece, Italy and the UK, and targeted stakeholders associated with pesticide exposure linked to orchards, greenhouse crops and arable crops respectively. The results indicated that the adoption of protective measures is low for residents and bystanders, with the exception of residents in Greece, when compared to operators and workers, who tend to follow recommended safety practices. A regression analysis was used to examine the factors affecting the probability of adopting protective measures as well the as the level of exposure in the case of operators and workers where data are available. The results indicate that the likelihood of engaging in self-protective behaviour is not significantly affected by perceptions of own health being affected by pesticides for residents and bystanders. However, operators who perceive that their heath has been negatively affected by the use of pesticides are found to be more likely to adopt self-protective behaviours. Gender and country differences, in perceptions, attitudes and self-protection are also observed. Recommendations for improved communication, in particular for vulnerable groups, are provided. PMID:25461109

  2. Observation of the Zero Doppler Effect

    PubMed Central

    Ran, Jia; Zhang, Yewen; Chen, Xiaodong; Fang, Kai; Zhao, Junfei; Chen, Hong

    2016-01-01

    The normal Doppler effect has well-established applications in many areas of science and technology. Recently, a few experimental demonstrations of the inverse Doppler effect have begun to appear in negative-index metamaterials. Here we report an experimental observation of the zero Doppler effect, that is, no frequency shift irrespective of the relative motion between the wave signal source and the detector in a zero-index metamaterial. This unique phenomenon, accompanied by the normal and inverse Doppler effects, is generated by reflecting a wave from a moving discontinuity in a composite right/left-handed transmission line loaded with varactors when operating in the near zero-index passband, or the right/left-handed passband. This work has revealed a complete picture of the Doppler effect in metamaterials and may lead to potential applications in electromagnetic wave related metrology. PMID:27046395

  3. Observation of the Zero Doppler Effect

    NASA Astrophysics Data System (ADS)

    Ran, Jia; Zhang, Yewen; Chen, Xiaodong; Fang, Kai; Zhao, Junfei; Chen, Hong

    2016-04-01

    The normal Doppler effect has well-established applications in many areas of science and technology. Recently, a few experimental demonstrations of the inverse Doppler effect have begun to appear in negative-index metamaterials. Here we report an experimental observation of the zero Doppler effect, that is, no frequency shift irrespective of the relative motion between the wave signal source and the detector in a zero-index metamaterial. This unique phenomenon, accompanied by the normal and inverse Doppler effects, is generated by reflecting a wave from a moving discontinuity in a composite right/left-handed transmission line loaded with varactors when operating in the near zero-index passband, or the right/left-handed passband. This work has revealed a complete picture of the Doppler effect in metamaterials and may lead to potential applications in electromagnetic wave related metrology.

  4. Observation of the Zero Doppler Effect.

    PubMed

    Ran, Jia; Zhang, Yewen; Chen, Xiaodong; Fang, Kai; Zhao, Junfei; Chen, Hong

    2016-01-01

    The normal Doppler effect has well-established applications in many areas of science and technology. Recently, a few experimental demonstrations of the inverse Doppler effect have begun to appear in negative-index metamaterials. Here we report an experimental observation of the zero Doppler effect, that is, no frequency shift irrespective of the relative motion between the wave signal source and the detector in a zero-index metamaterial. This unique phenomenon, accompanied by the normal and inverse Doppler effects, is generated by reflecting a wave from a moving discontinuity in a composite right/left-handed transmission line loaded with varactors when operating in the near zero-index passband, or the right/left-handed passband. This work has revealed a complete picture of the Doppler effect in metamaterials and may lead to potential applications in electromagnetic wave related metrology. PMID:27046395

  5. Predictors of Sexual Assault-Specific Prosocial Bystander Behavior and Intentions: A Prospective Analysis.

    PubMed

    Austin, Megan J Murphy; Dardis, Christina M; Wilson, Milo S; Gidycz, Christine A; Berkowitz, Alan D

    2016-01-01

    This study prospectively examined the impact of men's own attitudes and behaviors and perceptions of peer attitudes and behaviors on intentions and engagement in prosocial bystander behavior. Undergraduate men completed surveys at baseline and 4- and 7-month follow-ups. Men's perceptions of peer attitudes and behaviors and their own attitudes and behaviors were both important predictors of intentions. However, men's own attitudes and behaviors appeared to be more robustly predictive of behavior. Intentions to engage in bystander behavior were not predictive of behavior. Results support two specific areas of bystander intervention programming addressing misperceptions of social norms and personal attitudes and behaviors. PMID:26303402

  6. Observation of spin Hall effective field

    NASA Astrophysics Data System (ADS)

    Fan, Xin; Wu, Jun; Chen, Yunpeng; Jerry, Matthew; Zhang, Huaiwu; Xiao, John

    2013-03-01

    Recent development in spin Hall driven spin transfer torque has attracted intensive interests1. Liu et. al. has shown that the spin transfer torque induced by the spin Hall effect in a normal metal-ferromagnetic metal bilayer can switch the magnetization of the ferromagnetic layer, which may be a potential candidate for magnetic random access memory2. The switching of the magnetization was primarily attributed to the Slonczewski torque3. We show that besides the Slonczewski torque, the spin Hall effect also produces an effective field that can also facilitate the magnetization reversal. This effective field persists even with a Cu spacer layer, and reduces quickly with the increase of the ferromagnetic layer thickness. The observation of the spin Hall effective field shall have ramification on the understanding of both spin transfer torque and spin Hall effect. 1. K. Ando et. al., Electric manipulation of spin relaxation using the spin Hall effect, Physical Review Letters, 101, 036601 (2008). 2. L. Liu et. al., Spin-Torque Switching with the Giant Spin Hall Effect of Tantalum. Science 336, 555-558 (2012). 3. J. Slonczewski, Current-driven excitation of magnetic multilayers. Journal of Magnetism and Magnetic Materials, 159, L1-L7 (1996).

  7. Cytotoxic T Lymphocytes Derived from Patients with Chronic Hepatitis C Virus Infection Kill Bystander Cells via Fas-FasL Interaction

    PubMed Central

    Gremion, Christel; Grabscheid, Benno; Wölk, Benno; Moradpour, Darius; Reichen, Jürg; Pichler, Werner; Cerny, Andreas

    2004-01-01

    The role of Fas-mediated lysis of hepatocytes in hepatitis C virus (HCV)-induced injury is frequently discussed. We therefore analyzed the effect of the number of HCV antigen-expressing cells, the mode of antigen presentation, and the number of cytotoxic T lymphocytes in a coculture system mimicking cellular components of the liver. Here, we show that endogenously processed HCV proteins are capable of inducing bystander killing. We further demonstrate that 0.8 to 1.5% of cells presenting HCV antigens suffice to induce lysis of 10 to 29% of bystander cells, suggesting that the mechanism may be operative at low fractions of infected versus uninfected hepatocytes in vivo. Our data underscore the role of the Fas pathway in HCV-related liver injury and support the exploration of Fas-based treatment strategies for patients with chronic hepatitis C virus infection. PMID:14747581

  8. When can I help? A conceptual framework for the prevention of sexual violence through bystander intervention.

    PubMed

    McMahon, Sarah; Banyard, Victoria L

    2012-01-01

    The bystander intervention approach is gaining popularity as a means for engaging communities in sexual assault prevention, especially on college campuses. Many bystander programs are teaching community members how to intervene without first assisting them to identify the full range of opportunities when they can intervene. In this article, the authors review the literature on sexual violence bystander intervention and present a conceptual framework that lays out a continuum of bystander opportunities ranging from reactive situations after an assault has occurred, to situations before an assault has occurred (posing high to low risk to victims), as well as proactive situations where no risk to the victim is present. The implications of this typology are discussed in the context of program development, evaluation, and further research. PMID:22096017

  9. Being a Positive Bystander: Male Antiviolence Allies’ Experiences of “Stepping Up”

    PubMed Central

    Casey, Erin A.; Ohler, Kristin

    2014-01-01

    As bystander approaches become increasingly prevalent elements of sexual and domestic violence prevention efforts, it is necessary to better understand the factors that support or impede individuals in taking positive action in the face of aggressive or disrespectful behavior from others. This study presents descriptive findings about the bystander experiences of 27 men who recently became involved in antiviolence against women work. More specifically, we describe the consistency with which respondents actively intervene in the speech or behavior of others, the strategies they use, and the factors they weigh as they deliberate taking action. Respondents report a complex and interrelated set of individual and contextual influences on their choices within bystander opportunities, which hold implications for both violence-specific models of bystander behavior and for prevention intervention development. PMID:21859757

  10. Observations of wave effects on inlet circulation

    NASA Astrophysics Data System (ADS)

    Orescanin, Mara; Raubenheimer, Britt; Elgar, Steve

    2014-07-01

    Observations of water levels, winds, waves, and currents in Katama Bay, Edgartown Channel, and Katama Inlet on Martha's Vineyard, Massachusetts are used to test the hypothesis that wave forcing is important to circulation in inlet channels of two-inlet systems and to water levels in the bay between the inlets. Katama Bay is connected to the Atlantic Ocean via Katama Inlet and to Vineyard Sound via Edgartown Channel. A numerical model based on the momentum and continuity equations that uses measured bathymetry and is driven with observed water levels in the ocean and sound, ocean waves, and local winds predicts the currents observed in Katama Inlet more accurately when wave forcing is included than when waves are ignored. During Hurricanes Irene and Sandy, when incident (12-m water depth) significant wave heights were greater than 5 m, breaking-wave cross-shore (along-inlet-channel) radiation stress gradients enhanced flows from the ocean into the bay during flood tides, and reduced (almost to zero during Irene) flows out of the bay during ebb tides. Model simulations without the effects of waves predict net discharge from the sound to the ocean both during Hurricane Irene and over a 1-month period with a range of conditions. In contrast, simulations that include wave forcing predict net discharge from the ocean to the sound, consistent with the observations.

  11. Translating sexual assault prevention from a college campus to a United States military installation: piloting the know-your-power bystander social marketing campaign.

    PubMed

    Potter, Sharyn J; Stapleton, Jane G

    2012-05-01

    One population that shares both similar and different characteristics with traditional college-age students is the U.S. Military. Similarities include a high concentration of 18- to 26-year-olds dealing with new found independence, peer pressure, and the presence of social norms that support violence and hypermasculinity. Sexual violence is a major public health problem in the United States, and because of the similarities in the age group of college and military populations, the problems regarding sexual violence in both constituencies have been well-documented. In the current pilot study we seek to add to both current knowledge about and promising practices of translating prevention strategies from one target audience to another. We describe how we translated, administered, and evaluated a bystander intervention social marketing campaign focused on sexual assault prevention that had been found to significantly affect attitude change on a college campus for a U.S. Army installation in Europe. In addition to demonstrating the process of translating prevention strategies across target audiences, findings from this pilot study contribute to the evaluation data on the effectiveness of sexual violence prevention strategies implemented with members of the U.S. Military. From our analysis, we see that research participants indicate that the degree to which the images resonate with them and the familiarity of the context (i.e., social self-identification) significantly effect the participants' personal responsibility for reducing sexual assault, confidence in acting as a bystander, and reported engagement as a bystander. PMID:22080576

  12. Determinants of self-reported bystander behavior in cyberbullying incidents amongst adolescents.

    PubMed

    DeSmet, Ann; Veldeman, Charlene; Poels, Karolien; Bastiaensens, Sara; Van Cleemput, Katrien; Vandebosch, Heidi; De Bourdeaudhuij, Ilse

    2014-04-01

    This study explores behavioral determinants of self-reported cyberbullying bystander behavior from a behavioral change theoretical perspective, to provide levers for interventions. Nine focus groups were conducted with 61 young adolescents (aged 12-16 years, 52% girls). Assertive defending, reporting to others, providing advice, and seeking support were the most mentioned behaviors. Self-reported bystander behavior heavily depended on contextual factors, and should not be considered a fixed participant role. Bystanders preferred to handle cyberbullying offline and in person, and comforting the victim was considered more feasible than facing the bully. Most prevailing behavioral determinants to defend or support the victim were low moral disengagement, that the victim is an ingroup member, and that the bystander is popular. Youngsters felt they received little encouragement from their environment to perform positive bystanding behavior, since peers have a high acceptance for not defending and perceived parental support for defending behavior is largely lacking. These results suggest multilevel models for cyberbullying research, and interventions are needed. With much previous research into cyberbullying insufficiently founded in theoretical models, the employed framework of the Integrative Model and Social Cognitive Theory may inspire future studies into bystander behavior. PMID:24359305

  13. Bystanders' responses to offline bullying and cyberbullying: The role of empathy and normative beliefs about aggression.

    PubMed

    Machackova, Hana; Pfetsch, Jan

    2016-04-01

    Cyberbullying often takes place with the virtual presence or knowledge of bystanders. While we have some evidence about the determinants of bystanders' responses to offline bullying, we lack empirical studies concerning the variables that influence bystanders' responses to cyberbullying. The current study examines bystanders' responses to offline bullying and cyberbullying incidents. Two types of responses were captured: support toward the victims and the reinforcement of bullies' actions. Using data from 321 German adolescents (ages 12-18; M = 14.99; 44% girls), the association between bystanders' responses and normative beliefs about verbal aggression and cyberaggression, and affective and cognitive empathy, were tested in a path model. Both types of normative beliefs positively predicted the reinforcement of bullies, and normative belief about verbal aggression also predicted support for the victims of offline bullying. Both types of empathy predicted support in offline bullying, but only affective empathy predicted support in cyberbullying. There was no link between affective or cognitive empathy to the reinforcement of bullies. Moreover, bystanders' tendencies to respond supportively to the victim or to reinforce the bully were rather consistent in both cyber- and offline bullying, but there was no link between support and reinforcement. The findings are discussed with regard to implications for prevention and intervention efforts. PMID:26946454

  14. Call for research on bystander intervention to prevent sexual violence: the role of campus environments.

    PubMed

    McMahon, Sarah

    2015-06-01

    An important next step for the field is to determine what setting-level factors beyond the individual are critical to fostering campus environments that support pro-social, helpful bystander intervention action to prevent sexual violence. Therefore, the purpose of this paper is to provide a research agenda to investigate key areas of the campus environment and their potential influence on bystander intervention. To create the research agenda, a number of steps were followed including: (1) systematically reviewing the larger bystander literature to identify key environmental areas, (2) assessing what research is available specific to college campuses and sexual assault in each of these areas, and (3) outlining future research to address each of these areas on college campuses and determine their applicability to sexual violence situations. Five main groups of factors were found to influence bystander intervention beyond the individual, group and situational levels, including: social norms, sense of community, pro-social modeling, policies, and the physical environment. Certain areas of research on environmental influences on bystander intervention are more developed such as social norms, with little research on areas such as policies and the physical environment. However, further research is needed in each of the identified five areas to help identify how college campuses can support bystander intervention. PMID:25896230

  15. Cosmology with Peculiar Velocities: Observational Effects

    NASA Astrophysics Data System (ADS)

    Andersen, P.; Davis, T. M.; Howlett, C.

    2016-09-01

    In this paper we investigate how observational effects could possibly bias cosmological inferences from peculiar velocity measurements. Specifically, we look at how bulk flow measurements are compared with theoretical predictions. Usually bulk flow calculations try to approximate the flow that would occur in a sphere around the observer. Using the Horizon Run 2 simulation we show that the traditional methods for bulk flow estimation can overestimate the magnitude of the bulk flow for two reasons: when the survey geometry is not spherical (the data do not cover the whole sky), and when the observations undersample the velocity distributions. Our results may explain why several bulk flow measurements found bulk flow velocities that seem larger than those expected in standard ΛCDM cosmologies. We recommend a different approach when comparing bulk flows to cosmological models, in which the theoretical prediction for each bulk flow measurement is calculated specifically for the geometry and sampling rate of that survey. This means that bulk flow values will not be comparable between surveys, but instead they are comparable with cosmological models, which is the more important measure.

  16. The Role of Alcohol Consumption Patterns and Pro-Social Bystander Interventions in Contexts of Gender Violence.

    PubMed

    Fleming, Wm Michael; Wiersma-Mosley, Jacquelyn D

    2015-10-01

    Studies have shown that people differ in their likelihood of intervening as a bystander in situations of violence, but it is unclear how these actions relate to the use of alcohol. Two studies (N = 1,525) examined the relationship between alcohol use and pro-social bystander interventions in situations of physical and sexual coercion. Studies 1 and 2 provided cross-sectional evidence that alcohol use, along with alcohol expectancies, predicted patterns of bystander interventions, depending on gender. Discussion centers on the importance of including alcohol as another facet in understanding the role of pro-social bystander interventions. PMID:26175516

  17. Heart rate modulation in bystanding geese watching social and non-social events

    PubMed Central

    Wascher, Claudia A.F; Scheiber, Isabella B.R; Kotrschal, Kurt

    2008-01-01

    Simply observing other individuals interacting has been shown to affect subsequent behaviour and also hormones in ‘bystander’ individuals. However, immediate physiological responses of an observer have been hardly investigated. Here we present results on individuals' heart rate (HR) responses during various situations, which occur regularly in a flock of greylag geese (Anser anser, e.g. agonistic encounters, vehicles passing by). We recorded simultaneously HR and behaviour of 21 semi-tame free-roaming geese, equipped with fully implanted transmitters. We considered 304 social and 81 non-social events during which the focal individuals did not respond behaviourally. Independent of the spatial distance to the event, these HR responses were significantly greater in social contexts (e.g. departing or landing geese, agonistic interactions) than in non-social situations (e.g. vehicles passing by, thunder). Focal individuals showed a significantly higher maximum HR as well as a greater HR increase in response to agonistic interactions, in which the pair partner or a family member was involved, as compared with a non-affiliated goose. Also, HR was significantly higher when the bystander watched non-affiliated geese interacting, which were higher ranking than the focal. We conclude that these differences are due to different relevance of the recorded events for the focal individual, depending on the individuals involved in the observed interaction. PMID:18430645

  18. Supersymmetric Higgs singlet effects on FCNC observables

    SciTech Connect

    Hodgkinson, Robert N.

    2008-11-23

    Higgs singlet superflelds, usually present in extensions of the Minimal Supersymmetric Standard Model (MSSM) which address the {mu}-problem, such as the Next-to-Minimal Supersymmetric Standard Model (NMSSM) and the Minimal Nonminimal Supersymmetric Standard Model (mnSSM), can have significant contributions to B-meson flavour-changing neutral current observables for large values of tan{beta} > or approx. 50. Illustrative results are presented including effects on the B{sub s} and on the rare decay B{sub s}{yields}{mu}{sup +}{mu}{sup -}. In particular, we find that in the NMSSM, the branching ratio for B{sub s}{yields}{mu}{sup +}{mu}{sup -} can be enhanced or even suppressed with respect to the Standard Model prediction by more than one order of magnitude.

  19. Constraint effects observed in crack initiation stretch

    SciTech Connect

    Lambert, D.M.; Ernst, H.A.

    1995-12-31

    The current paper characterizes constraint in fracture: J-modified resistance (Jr) curves were developed for two tough structural materials, 6061-T651 (aluminum) and IN718-STA1 (nickel-base superalloy). A wide variety of configurations was tested to consider load configurations from bending to tension including three specimen types (compact tension, center-crack tension, and single-edge notched tension), and a range of ligament lengths and thicknesses, as well as side-grooved and smooth-sided ligaments. The Jr curves exhibited an inflection point after some crack extension, and the data were excluded beyond the inflection. Qualified Jr curves for the two materials showed similar behavior, but R-curves were identical for equal ligament length-to-thickness ratio (RL), for the aluminum alloy, with increasing slope for increasing RL, while for the nickel, the resistance curves aligned for equal ligament thickness, B, and the slope increased for decreasing B. Displacements at the original crack tip (CToD) were recorded throughout the test for several specimens. CToD-versus-crack extension curves were developed, and data were excluded beyond the inflection point (as with the Jr curves). The data collapsed into two distinct curves, thought to represent the surface, plane stress effect and the central, plane strain effect. This was observed for both materials. A technique called profiling is presented for the aluminum alloy only, where the crack face displacements are recorded at the final point of the test as a function of the position throughout the crack cavity, along with an effort to extract the observations in a usable form. Displacements were consistent throughout the cross-section at and behind the original crack tip. In the region where the crack grew, this displacement was developed by a combination of stretch and crack growth. The stretch required to initiate crack extension was a function of the depth beneath the surface into the cross-section.

  20. Observing System Variations Effect on Reanalyses

    NASA Technical Reports Server (NTRS)

    Bosilovich, Michael G.; Chen, Junye; Robertson, Franklin R.; da Silva, Arlindo

    2010-01-01

    Reanalyses integrate multitudes of satellite and conventional observations data assimilation and numerical weather prediction. The result is that many disparate observation platforms, discontinuous in space and time, lead to complete and consistent representations the state of the weather. The component also provides physical fields rarely or never observed. However, the numerical model bias is continuously being corrected by the observational analysis, and this bias changes as variations in the observations occur. NASA's Modern Era Retrospective-analysis for Research and Applications (MERRA) sensitivity to variations in the observing systems are explored. Specifically, we will evaluate the water budget and transport processes as they relate to the advent of SSM/I and AMSU-A radiance assimilation, and an additional case of radiosonde station that exhibits a dramatic shift in mean water states. The MERRA input observation data, now available online, is used to explore these variations.

  1. To act or not to act, that is the question? Barriers and facilitators of bystander intervention.

    PubMed

    Bennett, Sidney; Banyard, Victoria L; Garnhart, Lydia

    2014-02-01

    A promising line of inquiry in sexual violence prevention involves training potential bystanders to intervene in situations where there is risk for violence. Theories of bystander intervention often discuss barriers to helping behavior, but there has been little empirical inquiry into this question. We will present findings of a study of both barriers and facilitators of helping behavior in the context of sexual violence among first-semester college students. Two hundred and forty-two first year college students completed surveys during their first year of college. Measures included assessment of bystander behavior, perceived barriers to helping, as well as a variety of other variables identified in the literature as key correlates of helping. Quantitative and qualitative analyses were used to (a) describe barriers and facilitators of helping, (b) examine the relationship between barriers and self-reports of helping, and (c) model individual differences in helping behavior. In quantitative analyses, barriers, as assessed in this study, were better predictors of helping behavior directed at strangers than helping of friends. Results suggested that open-ended responses about the facilitators and barriers to helping for sexual violence map well onto social-psychological models of bystander behavior, and that greater prosocial tendencies, an intrapersonal variable, increase actual helping behavior. A more specific understanding of what promotes and hinders helping can be used to enhance prevention education efforts focused on increasing helpful bystander actions. PMID:24097909

  2. A randomized controlled trial of a multi-dose bystander intervention program using peer education theater.

    PubMed

    McMahon, Sarah; Winter, Samantha C; Palmer, Jane E; Postmus, Judy L; Peterson, N Andrew; Zucker, Sharon; Koenick, RuthAnne

    2015-08-01

    This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend norms and bystander behaviors) in situations involving sexual violence and whether there was a differential impact of the program by participant sex. First-year college students completed three waves of surveys (pretest, first post-test and second post-test). All participants received one dose of the intervention during summer orientation after the pretest. After the first post-test, participants were randomly assigned to receive two additional doses, or to a control condition, in which they received no additional doses. Students in both one- and three-dose groups reported a number of positive increases. Overall, an intent-to-treat analysis (n = 1390) indicated three doses of the intervention during the first semester of college resulted in better outcomes than the one-time intervention during summer orientation alone. Although both male and female students' scores increased during the study period, female students consistently scored higher than male students on each outcome. The findings suggest that peer education theater holds promise for bystander intervention education on college campuses. PMID:26135957

  3. Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics

    PubMed Central

    Kumar, Shari L.; Bhandari, Rohit K.; Kumar, Sunil D.

    2016-01-01

    The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA) is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR) saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p = 0.05), with a stronger disparity between low- and high-income neighborhoods (p = 0.01 and p = 0.03, resp.). Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p = 0.04). Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p = 0.03). Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all. PMID:27379186

  4. Innocent Bystanders and Smoking Guns: Dwarf Carbon Stars

    NASA Astrophysics Data System (ADS)

    Green, Paul J.

    2014-01-01

    As far as we know, most carbon throughout the Universe is created and dispersed by AGB stars. So it was at first surprising to find that the carbon stars most prevalent in the Galaxy are in fact dwarfs. We suspect that dC stars are most likely innocent bystanders in post-mass transfer binaries, and may be predominantly metal-poor. Among 1200 C stars found in the SDSS (Green 2013), we confirm 724 dCs, of which a dozen are DA/dC stars in composite spectrum binaries, quadrupling the total sample of these "smoking guns" for AGB binary mass transfer. The dCs likely span absolute magnitudes M_i from about 6.5 to 10.5. G-type dC stars with weak CN and relatively blue colors are probably the most massive dCs still cool enough to show C_2 bands. Eleven very red C stars with strong red CN bands appear to be N-type AGB stars at large Galactocentric distances, one likely a new discovery in the dIrr galaxy Le A. Two such stars within 30arcmin of each other may trace a previously unidentified dwarf galaxy or tidal stream at ~40 kpc. We describe follow-up projects to study the spatial, kinematic, and binary properties of these C-enriched dwarfs.

  5. Fungi in the cystic fibrosis lung: bystanders or pathogens?

    PubMed

    Chotirmall, Sanjay H; McElvaney, Noel G

    2014-07-01

    Improvement to the life expectancy of people with cystic fibrosis (PWCF) brings about novel challenges including the need for evaluation of the role of fungi in the cystic fibrosis (CF) lung. To determine if such organisms represent bystanders or pathogens affecting clinical outcomes we review the existing knowledge from a clinical, biochemical, inflammatory and immunological perspective. The prevalence and importance of fungi in the CF airway has likely been underestimated with the most frequently isolated filamentous fungi being Aspergillus fumigatus and Scedosporium apiospermum and the major yeast Candida albicans. Developing non-culture based microbiological methods for fungal detection has improved both our classification and understanding of their clinical consequences including localized, allergic and systemic infections. Cross-kingdom interaction between bacteria and fungi are discussed as is the role of biofilms further affecting clinical outcome. A combination of host and pathogen-derived factors determines if a particular fungus represents a commensal, colonizer or pathogen in the setting of CF. The underlying immune state, disease severity and treatment burden represent key host variables whilst fungal type, form, chronicity and virulence including the ability to evade immune recognition determines the pathogenic potential of a specific fungus at a particular point in time. Further research in this emerging field is warranted to fully elucidate the spectrum of disease conferred by the presence of fungi in the CF airway and the indications for therapeutic interventions. PMID:24625547

  6. A Longitudinal Study of the Associations between Moral Disengagement and Active Defending versus Passive Bystanding during Bullying Situations

    ERIC Educational Resources Information Center

    Doramajian, Caroline; Bukowski, William M.

    2015-01-01

    This study investigated the prospective association between moral disengagement and bystander behaviors in bullying situations, including both defending and passive bystanding. A diverse sample of Canadian school children (N = 130; 68 boys and 62 girls; mean age = 11.36 years) participated in a three-wave longitudinal study over a 4-month period.…

  7. Sorority Women's and Fraternity Men's Rape Myth Acceptance and Bystander Intervention Attitudes

    ERIC Educational Resources Information Center

    Bannon, R. Sean; Brosi, Matthew W.; Foubert, John D.

    2013-01-01

    Sorority women and fraternity men are more likely than other students to be survivors and perpetrators of sexual assault, respectively. The present study examined sorority and fraternity members' rape myth acceptance, bystander efficacy, and bystander willingness to help in potential sexual assault situations. Sorority women were more…

  8. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  9. Observational determination of the greenhouse effect

    NASA Technical Reports Server (NTRS)

    Raval, A.; Ramanathan, V.

    1989-01-01

    Satellite measurements are used to quantify the atmospheric greenhouse effect, defined here as the infrared radiation energy trapped by atmospheric gases and clouds. The greenhouse effect is found to increase significantly with sea surface temperature. The rate of increase gives compelling evidence for the positive feedback between surface temperature, water vapor and the greenhouse effect; the magnitude of the feedback is consistent with that predicted by climate models. This study demonstrates an effective method for directly monitoring, from space, future changes in the greenhouse effect.

  10. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  11. Observation assistants: sitter effectiveness and industry measures.

    PubMed

    Harding, Andrew D

    2010-01-01

    Patient safety remains a strategic goal and of societal importance for better health care. Direct observation remains an ineffective and expensive means of providing for patient safety. The nursing quality team found that using assessment tools helped to objectively categorize which patients are at risk. Defining patient volume, actual productive sitter usage, and assessing demand for patients in psychiatric crisis and patients at high risk to fall in the form of average daily census provided an easy-to-translate, familiar unit of measure to compare patient volume to demand and utilization. The sitter utilization case was unable to provide correlation of sitter use to decreased fall rates, elopement, or assault behaviors. Currently, there is no research to suggest the use of constant observation reduces the risk of patient harm related to their risk for falling or harming themselves. PMID:21158254

  12. Cosmogenic nuclides: Observable effects of Martian volatiles

    NASA Technical Reports Server (NTRS)

    Reedy, R. C.; Drake, D. M.; Feldman, W. C.

    1988-01-01

    Cosmic-ray produced (cosmogenic) nuclides in returned Martian samples could be used to study the amounts and distributions of volatiles in the recent past on Mars. In planning for the gamma-ray spectrometer experiment that is scheduled to fly on the Mars Observer, many calculations were done on the nuclear reactions that should occur in the Martian surface, studying especially the production and transport of neutrons. It is found that three aspects of Mars can very significantly affect the production of cosmogenic products in Mars: the Martian atmosphere and the presence of H2O in or CO2 on the surface of Mars. These volatile components can greatly affect the energy and spatial distributions of neutrons, expecially those with thermal or near thermal energies, in the surface of Mars. In turn, these neutrons produce many cosmogenic nuclides that can be observed in samples returned from Mars.

  13. Rindler effect for a nonuniformly accelerating observer

    SciTech Connect

    Zhu Jian-yang; Bao Aidong; Zhao Zheng

    1995-10-01

    Both the Klein-Gordon equation and the Dirac equation are dealt with in the generalized Rindler space-time of a nonuniformly accelerating observer. Making use of a new method and introducing a tortoise-type coordinate transformation, it is proved that there exist an event horizon and thermal radiation depending on time in the space-time. The Hawking-Unruh temperature is proportional to the variable acceleration.

  14. New risk indicator approach for Operators, Workers, Bystanders and Residents for a sustainable use of plant protection products.

    PubMed

    Sacchettini, Gabriele; Calliera, Maura; Marchis, Alexandru; Glass, Richard; Ellis, Clare Butler; Machera, Kyriaki; Gerritsen-Ebben, Rianda; Spanoghe, Pieter; Capri, Ettore

    2015-11-01

    In 2009, the European Union adopted the Directive on Sustainable Use of pesticides (SUD, Directive 2009/128/EC) establishing a framework for achieving a sustainable use of Plant Protection Products (PPPs) through reducing the risks and impacts of PPP use on human health and the environment, promoting integrated pest management and stimulating effective non-chemical alternatives. The core idea of the SUD is that it is necessary to monitor the use of PPPs through the implementation of an appropriate set of risk indicators to monitor progress and trends in risk reduction within the Member States. To contribute to this direction, following a comprehensive analysis of the risk (including procedures of risk assessment and risk management) and involving stakeholders in the decision process, specific toolboxes of practical indirect risk indicators of exposure of Operators, Workers, Bystanders and Residents were developed and are now available to be used by Member States (MSs) based on their specific context. PMID:26143544

  15. Conditioning of naive CD4(+) T cells for enhanced peripheral Foxp3 induction by nonspecific bystander inflammation.

    PubMed

    Thompson, Lucas J; Lai, Jen-Feng; Valladao, Andrea C; Thelen, Tennille D; Urry, Zoe L; Ziegler, Steven F

    2016-03-01

    Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This results in inhibition of immune responses in vivo via a Foxp3-dependent effect on antigen-specific naive CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the idea that early tuning of the immune system by infection affects the long-term quality of immune regulation. PMID:26752376

  16. Effective resolution concepts for lidar observations

    NASA Astrophysics Data System (ADS)

    Iarlori, M.; Madonna, F.; Rizi, V.; Trickl, T.; Amodeo, A.

    2015-12-01

    Since its establishment in 2000, EARLINET (European Aerosol Research Lidar NETwork) has provided, through its database, quantitative aerosol properties, such as aerosol backscatter and aerosol extinction coefficients, the latter only for stations able to retrieve it independently (from Raman or high-spectral-resolution lidars). These coefficients are stored in terms of vertical profiles, and the EARLINET database also includes the details of the range resolution of the vertical profiles. In fact, the algorithms used in the lidar data analysis often alter the spectral content of the data, mainly acting as low-pass filters to reduce the high-frequency noise. Data filtering is described by the digital signal processing (DSP) theory as a convolution sum: each filtered signal output at a given range is the result of a linear combination of several signal input data samples (relative to different ranges from the lidar receiver), and this could be seen as a loss of range resolution of the output signal. Low-pass filtering always introduces distortions in the lidar profile shape. Thus, both the removal of high frequency, i.e., the removal of details up to a certain spatial extension, and the spatial distortion produce a reduction of the range resolution. This paper discusses the determination of the effective resolution (ERes) of the vertical profiles of aerosol properties retrieved from lidar data. Large attention has been dedicated to providing an assessment of the impact of low-pass filtering on the effective range resolution in the retrieval procedure.

  17. Non-targeted effects of ionizing radiation–implications for low dose risk

    PubMed Central

    Kadhim, Munira; Salomaa, Sisko; Wright, Eric; Hildebrandt, Guido; Belyakov, Oleg V.; Prise, Kevin M.; Little, Mark P.

    2014-01-01

    Non-DNA targeted effects of ionizing radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionizing radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the Non-targeted effects of ionizing radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. PMID:23262375

  18. Reducing Sexual Violence on Campus: The Role of Student Leaders as Empowered Bystanders

    ERIC Educational Resources Information Center

    Banyard, Victoria L.; Moynihan, Mary M.; Crossman, Maria T.

    2009-01-01

    Sexual violence is a widespread problem for college communities. Students, faculty, and staff are increasingly involved in prevention efforts. To date, however, evaluation of sexual violence prevention programs has shown mixed results. One promising new practice teaches segments of college communities to be engaged, positive bystanders. It aims to…

  19. Using a Multimedia Social Marketing Campaign to Increase Active Bystanders on the College Campus

    ERIC Educational Resources Information Center

    Potter, Sharyn J.

    2012-01-01

    Objective: To evaluate the campus-wide administration of the Know Your Power bystander-oriented social marketing campaign. Participants: Undergraduate students at a public college were invited to participate in a public awareness survey before and after the 6-week campaign administration in February and March 2009. Methods: Pretest and posttests…

  20. Bystander Behavior in Bullying Situations: Basic Moral Sensitivity, Moral Disengagement and Defender Self-Efficacy

    ERIC Educational Resources Information Center

    Thornberg, Robert; Jungert, Tomas

    2013-01-01

    The aim of the present study was to investigate how basic moral sensitivity in bullying, moral disengagement in bullying and defender self-efficacy were related to different bystander behaviors in bullying. Therefore, we examined pathways that linked students' basic moral sensitivity, moral disengagement, and defender self-efficacy to different…

  1. Bystanders Matter: Associations between Reinforcing, Defending, and the Frequency of Bullying Behavior in Classrooms

    ERIC Educational Resources Information Center

    Salmivalli, Christina; Voeten, Marinus; Poskiparta, Elisa

    2011-01-01

    This study investigated whether the bystanders' behaviors (reinforcing the bully vs. defending the victim) in bullying situations are related to the frequency of bullying in a classroom. The sample consisted of 6,764 primary school children from Grades 3 to 5 (9-11 years of age), who were nested within 385 classrooms in 77 schools. The students…

  2. Determinants of Adolescents' Active Defending and Passive Bystanding Behavior in Bullying

    ERIC Educational Resources Information Center

    Gini, Gianluca; Albiero, Paolo; Benelli, Beatrice; Altoe, Gianmarco

    2008-01-01

    The literature on participant roles in bullying lacks empirical studies that seek to explain what differentiates defenders from outsiders (or passive bystanders). The present study tested a conceptual model in which two personal characteristics of early adolescent students (empathy and perceived social self-efficacy) were considered as possible…

  3. Being a Positive Bystander: Male Antiviolence Allies' Experiences of "Stepping up"

    ERIC Educational Resources Information Center

    Casey, Erin A.; Ohler, Kristin

    2012-01-01

    As bystander approaches become increasingly prevalent elements of sexual and domestic violence prevention efforts, it is necessary to better understand the factors that support or impede individuals in taking positive action in the face of aggressive or disrespectful behavior from others. This study presents descriptive findings about the…

  4. Participant Roles in Bullying: How Can Peer Bystanders Be Utilized in Interventions?

    ERIC Educational Resources Information Center

    Salmivalli, Christina

    2014-01-01

    This article provides a view of school bullying as a group phenomenon and practical implications stemming from this approach. The motivation for bullying perpetration often relates to one's social standing in the group. Peer bystanders are typically present when bullying takes place, often providing the perpetrators with social rewards. The…

  5. Bystander Responses to School Bullying: A Cross-Sectional Investigation of Grade and Sex Differences

    ERIC Educational Resources Information Center

    Trach, Jessica; Hymel, Shelley; Waterhouse, Terry; Neale, Ken

    2010-01-01

    Addressing the impact of peer bystanders on school bullying, this cross-sectional study examined whether student responses to bullying that they witnessed varied as a function of sex and grade. In a school-based survey regarding social experiences at school, Grade 4 to 11 students (N = 9397, 51% male) who reported witnessing bullying (68%) rated…

  6. Counseling and the Bystander-Equity Model of Supervisory Helping Behavior: Directions for EAP Research.

    ERIC Educational Resources Information Center

    Gerstein, Lawrence H.; Bayer, Gregory A.

    1991-01-01

    Discusses contribution of Bystander-Equity Model of Supervisory Helping Behavior to pursuit of employee assistance program (EAP) research based on traditions of field of counseling. Offers structure for pursuing empirical and applied activities in EAP settings. Encourages counseling researchers and practitioners to respond to challenge of working…

  7. The Role of Bystanders in Students' Perception of Bullying and Sense of Safety

    ERIC Educational Resources Information Center

    Gini, Gianluca; Pozzoli, Tiziana; Borghi, Francesco; Franzoni, Lara

    2008-01-01

    Two studies employing a mixed experimental design were conducted to determine if perceptions of bullying, attitudes towards victims, and students' sense of safety at school were influenced by bystanders' reactions to different types of bullying. In Study 1, 217 middle-school children were randomly assigned to read a hypothetical scenario…

  8. Bystanders to Bullying: Fourth-to Seventh-Grade Students' Perspectives on Their Reactions

    ERIC Educational Resources Information Center

    Forsberg, Camilla; Thornberg, Robert; Samuelsson, Marcus

    2014-01-01

    The aim with the present study was to investigate bystander actions in bullying situations as well as reasons behind these actions as they are articulated by Swedish students from fourth to seventh grade. Forty-three semi-structured individual interviews were conducted with students. Qualitative analysis of data was performed by methods from…

  9. R.U. Ready?: Peer Education and Bystander Intervention Sexual Assault Programming

    ERIC Educational Resources Information Center

    Schweer, Jen Luettel; Heather, Katie; Kay, Kathryn; Stewart, K. Leigh; Kovach, Laura

    2012-01-01

    R.U. Ready? at Georgetown University is an annual sexual assault awareness event that incorporates peer education and resources with opportunities for students, staff, and faculty to dialogue about providing bystander intervention throughout the campus community. Beyond dialogue, participants learn about student activism and the resources and…

  10. Bystander Intervention, Bullying, and Victimization: A Multilevel Analysis of New Zealand High Schools

    ERIC Educational Resources Information Center

    Denny, Simon; Peterson, Elizabeth R.; Stuart, Jaimee; Utter, Jennifer; Bullen, Pat; Fleming, Theresa; Ameratunga, Shanthi; Clark, Terryann; Milfont, Taciano

    2015-01-01

    This study examines the association between schools and student bullying behaviors and victimization among a nationally representative sample (N = 9,107) of New Zealand high school students. In particular, the study sought to explore the role of characteristics of schools and school culture with respect to bystander behavior, while controlling for…

  11. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  12. Validity for an integrated laboratory analogue of sexual aggression and bystander intervention.

    PubMed

    Parrott, Dominic J; Tharp, Andra Teten; Swartout, Kevin M; Miller, Cameron A; Hall, Gordon C Nagayama; George, William H

    2012-01-01

    This study sought to develop and validate an integrated laboratory paradigm of sexual aggression and bystander intervention. Participants were a diverse community sample (54% African American) of heterosexual males (N = 156) between 21 and 35 years of age who were recruited to complete the study with a male friend and an ostensibly single, heterosexual female who reported a strong dislike of sexual content in the media. Participants viewed a sexually explicit or nonsexually explicit film clip as part of contrived media rating task and made individual choices of which film clip to show the female confederate. Immediately thereafter, participants were required to reach consensus on a group decision of which film clip to show the female confederate. Subjecting a target to an unwanted experience with a sexual connotation was operationalized as selection of the sexually explicit video, whereas successful bystander intervention was operationalized as the event of one partner individually selecting the sexually explicit video but then selecting the nonsexually explicit video for the group choice. Results demonstrated that a 1-year history of sexual aggression and endorsement of pertinent misogynistic attitudes significantly predicted selection of the sexually-explicit video. In addition, bystander efficacy significantly predicted men's successful prevention of their male peer's intent to show the female confederate a sexually explicit video. Discussion focused on how these data inform future research and bystander intervention programming for sexual aggression. PMID:22549741

  13. Effective resolution concepts for lidar observations

    NASA Astrophysics Data System (ADS)

    Iarlori, M.; Madonna, F.; Rizi, V.; Trickl, T.; Amodeo, A.

    2015-05-01

    Since its first establishment in 2000, EARLINET (European Aerosol Research Lidar NETwork) has been devoted to providing, through its database, exclusively quantitative aerosol properties, such as aerosol backscatter and aerosol extinction coefficients, the latter only for stations able to retrieve it independently (from Raman or High Spectral Resolution Lidars). As these coefficients are provided in terms of vertical profiles, EARLINET database must also include the details on the range resolution of the submitted data. In fact, the algorithms used in the lidar data analysis often alter the spectral content of the data, mainly working as low pass filters with the purpose of noise damping. Low pass filters are mathematically described by the Digital Signal Processing (DSP) theory as a convolution sum. As a consequence, this implies that each filter's output, at a given range (or time) in our case, will be the result of a linear combination of several lidar input data relative to different ranges (times) before and after the given range (time): a first hint of loss of resolution of the output signal. The application of filtering processes will also always distort the underlying true profile whose relevant features, like aerosol layers, will then be affected both in magnitude and in spatial extension. Thus, both the removal of noise and the spatial distortion of the true profile produce a reduction of the range resolution. This paper provides the determination of the effective resolution (ERes) of the vertical profiles of aerosol properties retrieved starting from lidar data. Large attention has been addressed to provide an assessment of the impact of low-pass filtering on the effective range resolution in the retrieval procedure.

  14. Emergency dispatch process and patient outcome in bystander-witnessed out-of-hospital cardiac arrest with a shockable rhythm

    PubMed Central

    Silfvast, Tom O.; Jäntti, T. Helena; Kuisma, Markku J.; Kurola, Jouni O.

    2015-01-01

    Objective To describe the dispatch process for out-of-hospital cardiac arrest (OHCA) in bystander-witnessed patients with initial shockable rhythm, and to evaluate whether recognition of OHCA by the emergency medical dispatcher (EMD) has an effect on the outcome. Methods This study was part of the FINNRESUSCI study focusing on the epidemiology and outcome of OHCA in Finland. Witnessed [not by Emergency Medical Service (EMS)] OHCA patients with initial shockable rhythm in the southern and the eastern parts of Finland during a 6-month period from March 1 to August 31 2010, were electronically collected from eight dispatch centres and from paper case reports filled out by EMS crews. Results Of the 164 patients, 82.3% (n=135) were correctly recognized by the EMD as cardiac arrests. The majority of all calls (90.7%) were dispatched within 2 min. Patients were more likely to survive and be discharged from the hospital if the EMS response time was within 8 min (P<0.001). Telephone-guided cardiopulmonary resuscitation (T-CPR) was given in 53 cases (32.3%). Overall survival to hospital discharge was 43.4% (n=71). Survival to hospital discharge was 44.4% (n=60) when the EMD recognized OHCA and 37.9% (n=11) when OHCA was not recognized. The difference was not statistically significant (P=0.521). Conclusion The rate of recognition of cardiac arrest by EMD was high, but EMD recognition did not affect the outcome. The survival rate was high in both groups. Recognized cardiac arrest patients received bystander CPR more frequently than those for whom OHCA remained unrecognized. PMID:24809817

  15. Gravity Effects Observed In Partially Premixed Flames

    NASA Technical Reports Server (NTRS)

    Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Gauguly, Ranjan; Hegde, Uday

    2003-01-01

    Partially premixed flames (PPFs) contain a rich premixed fuel air mixture in a pocket or stream, and, for complete combustion to occur, they require the transport of oxidizer from an appropriately oxidizer-rich (or fuel-lean) mixture that is present in another pocket or stream. Partial oxidation reactions occur in fuel-rich portions of the mixture and any remaining unburned fuel and/or intermediate species are consumed in the oxidizer-rich portions. Partial premixing, therefore, represents that condition when the equivalence ratio (phi) in one portion of the flowfield is greater than unity, and in another section its value is less than unity. In general, for combustion to occur efficiently, the global equivalence ratio is in the range fuel-lean to stoichiometric. These flames can be established by design by placing a fuel-rich mixture in contact with a fuel-lean mixture, but they also occur otherwise in many practical systems, which include nonpremixed lifted flames, turbulent nonpremixed combustion, spray flames, and unwanted fires. Other practical applications of PPFs are reported elsewhere. Although extensive experimental studies have been conducted on premixed and nonpremixed flames under microgravity, there is a absence of previous experimental work on burner stabilized PPFs in this regard. Previous numerical studies by our group employing a detailed numerical model showed gravity effects to be significant on the PPF structure. We report on the results of microgravity experiments conducted on two-dimensional (established on a Wolfhard-Parker slot burner) and axisymmetric flames (on a coannular burner) that were investigated in a self-contained multipurpose rig. Thermocouple and radiometer data were also used to characterize the thermal transport in the flame.

  16. Effects of high-dose microbeam irradiation on tumor microvascular function and angiogenesis.

    PubMed

    Fontanella, Andrew N; Boss, Mary-Keara; Hadsell, Michael; Zhang, Jian; Schroeder, Thies; Berman, Katherine G; Dewhirst, Mark W; Chang, Sha; Palmer, Gregory M

    2015-02-01

    Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects. PMID:25574586

  17. Effects of High-Dose Microbeam Irradiation on Tumor Microvascular Function and Angiogenesis

    PubMed Central

    Fontanella, Andrew N.; Boss, Mary-Keara; Hadsell, Michael; Zhang, Jian; Schroeder, Thies; Berman, Katherine G.; Dewhirst, Mark W.; Chang, Sha; Palmer, Gregory M.

    2015-01-01

    Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects. PMID:25574586

  18. Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes.

    PubMed

    Cheung, Wing Yee; Fritton, J Christopher; Morgan, Stacy Ann; Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Thi, Mia M; Suadicani, Sylvia O; Spray, David C; Majeska, Robert J; Schaffler, Mitchell B

    2016-04-01

    Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring "bystander" cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a "find-me" signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-κB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7 R in ATP release; thus, we examined P2X7 R-deficient mice and WT mice treated with P2X7 R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7 RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X7 RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7 R are required for apoptotic osteocytes

  19. The effects of stereotypes and observer pressure on athletic performance.

    PubMed

    Krendl, Anne; Gainsburg, Izzy; Ambady, Nalini

    2012-02-01

    Although the effects of negative stereotypes and observer pressure on athletic performance have been well researched, the effects of positive stereotypes on performance, particularly in the presence of observers, is not known. In the current study, White males watched a video either depicting Whites basketball players as the best free throwers in the NBA (positive stereotype), Black basketball players as the best free throwers in the NBA (negative stereotype), or a neutral sports video (control). Participants then shot a set of free throws, during which half the participants were also videotaped (observer condition), whereas the other half were not (no observer condition). Results demonstrated that positive stereotypes improved free throw performance, but only in the no observer condition. Interestingly, observer pressure interacted with the positive stereotype to lead to performance decrements. In the negative stereotype condition, performance decrements were observed both in the observer and no observer conditions. PMID:22356881

  20. Victim Reports of Bystander Reactions to In-Person and Online Peer Harassment: A National Survey of Adolescents.

    PubMed

    Jones, Lisa M; Mitchell, Kimberly J; Turner, Heather A

    2015-12-01

    Bullying prevention is increasingly targeting education to bystanders, but more information is needed on the complexities of bystander actions across a wide variety of incidents, including both online and in-person peer harassment. The current study analyzes victim report data from a nationally representative survey of youth ages 10-20 (n = 791; 51% female). Bystander presence was common across all harassment incident types (80% of incidents). In contrast to previous research, our study found that supportive bystander behaviors occurred at relatively high rates. Unfortunately, antagonistic bystander behaviors, although less common, were predictive of higher negative impact for the victim. A large percentage of victims (76%) also disclosed the harassment to confidants, who play an important role as secondary bystanders. While friends were the most common confidant, incidents were also disclosed to adults at high rates (60%) and with mostly positive results. The findings suggest that prevention programs could increase their impact by targeting education to both direct witnesses and confidants, and considering a wider variety of peer victimization incident types. PMID:26316304

  1. Efficacy of Bystander Programs to Prevent Dating Abuse Among Youth and Young Adults: A Review of the Literature.

    PubMed

    Storer, Heather L; Casey, Erin; Herrenkohl, Todd

    2016-07-01

    Estimates suggest that between 10% and 25% of adolescents have experienced some form of physical violence within a dating relationship, and one in four college-age women experiences attempted or completed sexual violence on campus. Bystander programs focus on equipping young adults with the skills to safely intervene when they witness behaviors that can result in dating abuse. This approach is promoted for its capacity both to transform community norms that contribute to dating abuse and to foster more positive social interactions among youth, however, there has been limited review of the literature on the outcomes of bystander programs. Therefore, this article provides an in-depth systematic literature review, which describes the content and program components of bystander programs and summarizes what is currently known about the impact of bystander interventions on participants' behaviors and attitudes. Results indicate that bystander programs are promising from the standpoint of increasing young adults' willingness to intervene and confidence in their ability to intervene when they witness dating or sexual violence, however, the utilization of actual bystander behaviors was less straightforward. Implications for prevention practice and for future research are presented. PMID:25951840

  2. Dendritic cells and NK cells stimulate bystander T cell activation in response to TLR agonists through secretion of IFN-alpha beta and IFN-gamma.

    PubMed

    Kamath, Arun T; Sheasby, Christopher E; Tough, David F

    2005-01-15

    Recognition of conserved features of infectious agents by innate pathogen receptors plays an important role in initiating the adaptive immune response. We have investigated early changes occurring among T cells after injection of TLR agonists into mice. Widespread, transient phenotypic activation of both naive and memory T cells was observed rapidly after injection of molecules acting through TLR3, -4, -7, and -9, but not TLR2. T cell activation was shown to be mediated by a combination of IFN-alphabeta, secreted by dendritic cells (DCs), and IFN-gamma, secreted by NK cells; notably, IFN-gamma-secreting NK cells expressed CD11c and copurified with DCs. Production of IFN-gamma by NK cells could be stimulated by DCs from TLR agonist-injected mice, and although soluble factors secreted by LPS-stimulated DCs were sufficient to induce IFN-gamma, maximal IFN-gamma production required both direct contact of NK cells with DCs and DC-secreted cytokines. In vitro, IFN-alphabeta, IL-18, and IL-12 all contributed to DC stimulation of NK cell IFN-gamma, whereas IFN-alphabeta was shown to be important for induction of T cell bystander activation and NK cell IFN-gamma production in vivo. The results delineate a pathway involving innate immune mediators through which TLR agonists trigger bystander activation of T cells. PMID:15634897

  3. Absent bystanders and cognitive dissonance: a comment on Timmins & de Vries.

    PubMed

    Paley, John

    2015-04-01

    Timmins & de Vries are more sympathetic to my editorial than other critics, but they take issue with the details. They doubt whether the bystander phenomenon applies to Mid Staffs nurses; they believe that cognitive dissonance is a better explanation of why nurses fail to behave compassionately; and they think that I am 'perhaps a bit rash' to conclude that 'teaching compassion may be fruitless'. In this comment, I discuss all three points. I suggest that the bystander phenomenon is irrelevant; that Timmins & de Vries give an incomplete account of cognitive dissonance; and that it isn't rash to propose that educating nurses 'for compassion' is a red herring. Additionally, I comment on the idea that I wish to mount a 'defence of healthcare staff'. PMID:25549986

  4. Chimpanzees' Bystander Reactions to Infanticide: An Evolutionary Precursor of Social Norms?

    PubMed

    von Rohr, Claudia Rudolf; van Schaik, Carel P; Kissling, Alexandra; Burkart, Judith M

    2015-06-01

    Social norms-generalized expectations about how others should behave in a given context-implicitly guide human social life. However, their existence becomes explicit when they are violated because norm violations provoke negative reactions, even from personally uninvolved bystanders. To explore the evolutionary origin of human social norms, we presented chimpanzees with videos depicting a putative norm violation: unfamiliar conspecifics engaging in infanticidal attacks on an infant chimpanzee. The chimpanzees looked far longer at infanticide scenes than at control videos showing nut cracking, hunting a colobus monkey, or displays and aggression among adult males. Furthermore, several alternative explanations for this looking pattern could be ruled out. However, infanticide scenes did not generally elicit higher arousal. We propose that chimpanzees as uninvolved bystanders may detect norm violations but may restrict emotional reactions to such situations to in-group contexts. We discuss the implications for the evolution of human morality. PMID:26108616

  5. Video calls from lay bystanders to dispatch centers - risk assessment of information security

    PubMed Central

    2011-01-01

    Background Video calls from mobile phones can improve communication during medical emergencies. Lay bystanders can be instructed and supervised by health professionals at Emergency Medical Communication Centers. Before implementation of video mobile calls in emergencies, issues of information security should be addressed. Methods Information security was assessed for risk, based on the information security standard ISO/IEC 27005:2008. A multi-professional team used structured brainstorming to find threats to the information security aspects confidentiality, quality, integrity, and availability. Results Twenty security threats of different risk levels were identified and analyzed. Solutions were proposed to reduce the risk level. Conclusions Given proper implementation, we found no risks to information security that would advocate against the use of video calls between lay bystanders and Emergency Medical Communication Centers. The identified threats should be used as input to formal requirements when planning and implementing video calls from mobile phones for these call centers. PMID:21958387

  6. Outcomes of a Bystander Intervention Community Health Service-Learning Project.

    PubMed

    Decker, Kim; Hensel, Desiree; Fasone, Leslie

    2016-01-01

    The purpose of this article is to describe the integration of a college bystander intervention service-learning project into an entry-level community clinical course in a prelicensure program and its outcomes. Two years of data from 118 students showed that students helped improve campus safety while growing as professionals and gaining leadership and health promotion skills. Approximately one-third of the students described a specific incident in which they intervened in an ambiguous situation. PMID:26633150

  7. Non-targeted radiation effects in vertebrate cell lines

    NASA Astrophysics Data System (ADS)

    Ryan, Lorna

    Radiation effects, such as bystander effects, hyper radiosensitivity/induced radioresistance (HRS/IRR) and adaptive response that are not related to direct DNA damage are now accepted. However the inter-relationship between them and the possible impact on the scientific basis for radiation protection are highly controversial. This thesis attempts to elucidate the mechanisms of some of these well known but little understood effects. Each paper examines some aspect of bystander effects, adaptive responses and HRS/IRR in an effort to understand how they vary with cell type, dose and time of exposure to single or multiple doses. All the effects involve non-linear dose effect curves and are mainly evident following low doses. Overall findings of the thesis include (1) A clear difference was observed between radioresistant, tumorigenic cell lines with mutant p53 gene expression, and radiosensitive, more normal, cell lines with wild type p53. In general death inducing bystander responses are induced in normal cell populations exposed to low doses of radiation while survival inducing IRR and adaptive responses are seen in the radioresistant tumorigenic cell lines. (2) A cohort of fish cell lines which demonstrated survival promoting bystander effects, also did not show a protective adaptive responses. (3) Adaptive responses traditionally occur when a large challenge dose is given 4--6hrs following low (10--100mGy) priming doses but this thesis shows that for the epithelial cell lines tested, the size of the priming dose (range 0.1--2Gy) does not appear to alter the size of the recovery response. Additionally increased survival could be detected in some cases when the challenge dose was given within one hour of the priming dose. The overall conclusion is that cell lines induce either a bystander response or a protective/adaptive response depending on genetic background and other factors. Care is needed in the interpretation of data generated from only one or two cell lines

  8. Gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in targeted and bystander human artificial skin models and peripheral blood lymphocytes

    NASA Astrophysics Data System (ADS)

    Redon, Christophe; Dickey, Jennifer; Bonner, William; Sedelnikova, Olga

    30 min after irradiation and then declined at a relatively steady pace as the cell repaired the DNA damage. Radiation effects were still detectable after 48 hrs for doses greater than 1 Gy and remained linear to initial dose. Activated bystander lymphocytes cultured with media from irradiated lymphocytes exhibited a two-fold increased damage response as seen by gamma- H2AX formation. The effect reached a maximum 3 hrs post-exposure and was retained for over 24 hrs. Thus, detection of gamma-H2AX formation to determine DNA damage in a minimally invasive skin test and a non-invasive blood test could be useful and promising tools to analyze direct and indirect effects of radiation exposure.

  9. Bystanding an abused child: testing the applicability of the stages of change construct.

    PubMed

    Mudde, Aart N; Hoefnagels, Cees J; Van Wijnen, Lisa G C; Kremers, Stef P J

    2007-02-01

    A minority of child abuse cases is recognized by professionals, making the role of non-professional bystanders essential. The stages of change construct, as proposed by the Transtheoretical Model, may provide a useful approach to explain non-professional helping behavior. The objective of this study was to test the applicability of the stages of change construct by (i) assessing whether cognitive determinants distinguish between the stages, (ii) testing the predictive value of the stages for future helping behavior and (iii) examining the mediating role of the stages in the relation between previous and future helping behavior. Data of 126 adult non-professional bystanders were analyzed. Respondents were questioned by telephone or via an Internet questionnaire, at baseline and after a follow-up of about two months later. Attitude toward helping was significantly less positive in pre-contemplation than in the other stages, and self-efficacy expectations were significantly higher in preparation compared with the other stages. Moreover, baseline preparators were more likely to conduct future helping behavior than those in the two earlier stages. Finally, the stages of change mediated the relation between previous and future helping behavior. Initial support was found for the applicability of the stages of change construct for helping behavior by non-professional bystanders. PMID:16849390

  10. Values in Action: Observations of Effective Principals at Work

    ERIC Educational Resources Information Center

    Parkes, Sharon E.; Thomas, A. Ross

    2007-01-01

    Purpose: The purpose of this research is to report on the values practised by five effective secondary principals and to seek to identify common values that underpin their work practices. Design/methodology/approach: Principals were observed, each for two days, at work in their schools. From the observations of each principal activities were…

  11. Observation and Recording Effects on Group Therapy Client Behaviors.

    ERIC Educational Resources Information Center

    Berman, Alan L.; Decker, Robert E.

    This study assesses the effect of visual versus audio observation/recording on both client and therapist verbal and non-verbal behavior in ongoing therapy. Three co-led, therapy groups were studied over six weekly sessions under counterbalanced observation conditions. Measures of verbal behavior, verbal productivity, and non-verbal behavior were…

  12. Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander".

    PubMed

    Gelao, Lucia; Criscitiello, Carmen; Esposito, Angela; Goldhirsch, Aron; Curigliano, Giuseppe

    2014-03-01

    Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment. PMID:24594636

  13. Bystander position taking in school bullying: the role of positive identity, self-efficacy, and self-determination.

    PubMed

    Tsang, Sandra K M; Hui, Eadaoin K P; Law, Bella C M

    2011-01-01

    School bullying has become an explicit, burgeoning problem challenging the healthy development of children and adolescents in Hong Kong. Many bullying prevention and intervention programs focus on victims and bullies, with bystanders treated as either nonexistent or irrelevant. This paper asserts that bystanders actually play pivotal roles in deciding whether the bullying process and dynamics are benign or adversarial. Bystanders' own abilities and characteristics often influence how they respond to victims and bullies. "P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme" (P.A.T.H.S. = Positive Adolescent Training through Holistic Social Programmes) is an evidence-based positive youth development program which shows that primary intervention programs have constructive impacts on junior secondary school students' beliefs and behavior. This paper asserts that intrapsychic qualities, namely identity, self-efficacy, and self-determination, greatly influence how bystanders react in school bullying situations. The paper also explains how classroom-based educational programs based on the P.A.T.H.S. model have been designed to help junior secondary school students strengthen these characteristics, so that they can be constructive bystanders when they encounter school bullying. PMID:22194663

  14. Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

    PubMed Central

    Cervellin, Gianfranco; Comelli, Ivan; Buonocore, Ruggero; Picanza, Alessandra; Rastelli, Gianni; Lippi, Giuseppe

    2015-01-01

    OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years). Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001) was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning. PMID:26375565

  15. Educating for Justice: Creating a Mission-Driven Model of Bystander Intervention to Address Sexual Violence at U.S. Catholic Colleges and Universities

    ERIC Educational Resources Information Center

    Galarneau, Joy; O'Neill, Shannon

    2015-01-01

    This article presents bystander intervention education as a best-practice approach to sexual violence prevention in college settings. It draws out a connection between mission-specific resources that can be used to advance the prevention agenda, while examining how bystander intervention education can deepen community engagement in collegiate…

  16. The effect of social observation on children's inhibitory control.

    PubMed

    Moriguchi, Yusuke

    2012-10-01

    This study examined the effects of social observation on young children's performance during an inhibitory control task. In Experiment 1, children were randomly assigned to either a neutral, facilitation, or interference condition. In the neutral condition, children were presented with a standard black/white task. In the facilitation and interference conditions, children were asked to observe the task performance of another person, who gave either correct (facilitation) or incorrect (interference) responses, and then complete the task themselves. The results revealed that the performance of children in the interference condition was worse than in the other two conditions, but the difference between the two other conditions was not significant. The results of Experiment 2 show that social observation did not facilitate inhibitory control in children. These results suggest that social observation interferes with but does not facilitate inhibitory control in children. Therefore, social observation may interfere with certain aspects of executive function. PMID:22781163

  17. Geometric effects in SeaWiFS lunar observations

    NASA Astrophysics Data System (ADS)

    Eplee, Robert E.; Patt, Frederick S.; Meister, Gerhard

    2015-09-01

    The radiometric stability requirements for ocean color climate data records place tight constraints on the onorbit calibration of ocean color instruments. A major component of the on-orbit calibration methodology for NASA ocean color sensors is the normalization of lunar observations for variations in observing geometry by the USGS ROLO photometric model of the Moon. SeaWiFS made 204 lunar observations over its 13-year mission. 145 radiometric trending observations were made at low phase angles (-8° to -6° and +5° to +10°). 59 additional observations were made at high phase angles (-49° to -27° and +27° to +66° degrees). The NASA Ocean Biology Processing Group has undertaken a reanalysis of residual geometric effects in the SeaWiFS lunar observations. Ratios of SeaWiFS observations to ROLO model predictions were fit with quadratic functions of phase angle and linear functions of sub-spacecraft point and sub-solar point libration longitude and latitude angles. The resulting phase and libration fit coefficients have been used as additional geometric corrections for the SeaWiFS lunar observations. For the low phase angle observations, the phase corrections are 0.16% and the libration corrections are 0.18%. For the low and high phase angle observations, the phase corrections are 1.8% and the libration corrections are 0.22%. These geometric corrections have reduced the overall scatter in the lunar observations, bringing the high phase angle data into family with the low phase angle measurements without impacting the radiometric response in the low phase angle observations.

  18. Probing the effect of OSCE checklist length on inter-observer reliability and observer accuracy

    PubMed Central

    Hurley, Katrina F.; Giffin, Nick A.; Stewart, Samuel A.; Bullock, Graham B.

    2015-01-01

    Purpose The Objective Structured Clinical Examination (OSCE) is a widely employed tool for measuring clinical competence. In the drive toward comprehensive assessment, OSCE stations and checklists may become increasingly complex. The objective of this study was to probe inter-observer reliability and observer accuracy as a function of OSCE checklist length. Method Study participants included emergency physicians and senior residents in Emergency Medicine at Dalhousie University. Participants watched an identical series of four, scripted, standardized videos enacting 10-min OSCE stations and completed corresponding assessment checklists. Each participating observer was provided with a random combination of two 40-item and two 20-item checklists. A panel of physicians scored the scenarios through repeated video review to determine the ‘gold standard’ checklist scores. Results Fifty-seven observers completed 228 assessment checklists. Mean observer accuracy ranged from 73 to 93% (14.6–18.7/20), with an overall accuracy of 86% (17.2/20), and inter-rater reliability range of 58–78%. After controlling for station and individual variation, no effect was observed regarding the number of checklist items on overall accuracy (p=0.2305). Consistency in ratings was calculated using intraclass correlation coefficient and demonstrated no significant difference in consistency between the 20- and 40-item checklists (ranged from 0.432 to 0.781, p-values from 0.56 to 0.73). Conclusions The addition of 20 checklist items to a core list of 20 items in an OSCE assessment checklist does not appear to impact observer accuracy or inter-rater reliability. PMID:26490948

  19. OBSERVING GRAVITATIONAL LENSING EFFECTS BY Sgr A* WITH GRAVITY

    SciTech Connect

    Bozza, V.; Mancini, L. E-mail: mancini@mpia-hd.mpg.de

    2012-07-01

    The massive black hole Sgr A* at the Galactic center is surrounded by a cluster of stars orbiting around it. Light from these stars is bent by the gravitational field of the black hole, giving rise to several phenomena: astrometric displacement of the primary image, the creation of a secondary image that may shift the centroid of Sgr A*, and magnification effects on both images. The soon-to-be second-generation Very Large Telescope Interferometer instrument GRAVITY will perform observations in the near-infrared of the Galactic center at unprecedented resolution, opening the possibility of observing such effects. Here we investigate the observability limits for GRAVITY of gravitational lensing effects on the S-stars in the parameter space 1[D{sub LS}, {gamma}, K], where D{sub LS} is the distance between the lens and the source, {gamma} is the alignment angle of the source, and K is the source's apparent magnitude in the K band. The easiest effect to observe in future years is the astrometric displacement of primary images. In particular, the shift of the star S17 from its Keplerian orbit will be detected as soon as GRAVITY becomes operative. For exceptional configurations, it will be possible to detect effects related to the spin of the black hole or post-Newtonian orders in the deflection.

  20. Observing Gravitational Lensing Effects by Sgr A* with GRAVITY

    NASA Astrophysics Data System (ADS)

    Bozza, V.; Mancini, L.

    2012-07-01

    The massive black hole Sgr A* at the Galactic center is surrounded by a cluster of stars orbiting around it. Light from these stars is bent by the gravitational field of the black hole, giving rise to several phenomena: astrometric displacement of the primary image, the creation of a secondary image that may shift the centroid of Sgr A*, and magnification effects on both images. The soon-to-be second-generation Very Large Telescope Interferometer instrument GRAVITY will perform observations in the near-infrared of the Galactic center at unprecedented resolution, opening the possibility of observing such effects. Here we investigate the observability limits for GRAVITY of gravitational lensing effects on the S-stars in the parameter space 1[D LS, γ, K], where D LS is the distance between the lens and the source, γ is the alignment angle of the source, and K is the source's apparent magnitude in the K band. The easiest effect to observe in future years is the astrometric displacement of primary images. In particular, the shift of the star S17 from its Keplerian orbit will be detected as soon as GRAVITY becomes operative. For exceptional configurations, it will be possible to detect effects related to the spin of the black hole or post-Newtonian orders in the deflection.

  1. Observation of an inductive-like effect in a supercapacitor

    NASA Astrophysics Data System (ADS)

    Kovalyuk, Z. D.; Yurtsenyuk, S. P.; Semenchuk, I. I.

    2016-03-01

    A supercapacitor with two identical activated pyrolytic carbon electrodes prepared by pyrolysis of raw plant material has been studied. The transition from charge to discharge and vice versa in a partly charged capacitor is accompanied by an inductive-like effect. The magnitude of apparent induction has been determined. It is suggested that the observed effect can be determined by the kinetics of ions in the electrolyte solution filling porous structure of the electrode material.

  2. The Effect of Social Observation on Children's Inhibitory Control

    ERIC Educational Resources Information Center

    Moriguchi, Yusuke

    2012-01-01

    This study examined the effects of social observation on young children's performance during an inhibitory control task. In Experiment 1, children were randomly assigned to either a neutral, facilitation, or interference condition. In the neutral condition, children were presented with a standard black/white task. In the facilitation and…

  3. The Effects of Commercial Airline Traffic on LSST Observing Efficiency

    NASA Astrophysics Data System (ADS)

    Gibson, Rose; Claver, Charles; Stubbs, Christopher

    2016-01-01

    The Large Synoptic Survey Telescope (LSST) is a ten-year survey that will map the southern sky in six different filters 800 times before the end of its run. In this paper, we explore the primary effect of airline traffic on scheduling the LSST observations in addition to the secondary effect of condensation trails, or contrails, created by the presence of the aircraft. The large national investment being made in LSST implies that small improvments observing efficiency through aircraft and contrail avoidance can result in a significant improvement in the quality of the survey and its science. We have used the Automatic Dependent Surveillance-Broadcast (ADS-B) signals received from commercial aircraft to monitor and record activity over the LSST site. We installed a ADS-B ground station on Cerro Pachón, Chile consiting of a1090Mhz antenna on the Andes Lidar Observatory feeding a RTL2832U software defined radio. We used dump1090 to convert the received ADS-B telementry into Basestation format, where we found that during the busiest time of the night there were only 4 signals being received each minute on average, which will have very small direct effect, if any, on the LSST observing scheduler. As part of future studies we will examin the effects of contrals on LSST observations. Gibson was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experience for Undergraduates Program (AST-1262829).

  4. Bystander responses to a violent incident in an immersive virtual environment.

    PubMed

    Slater, Mel; Rovira, Aitor; Southern, Richard; Swapp, David; Zhang, Jian J; Campbell, Claire; Levine, Mark

    2013-01-01

    Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation. PMID:23300991

  5. Bystander Responses to a Violent Incident in an Immersive Virtual Environment

    PubMed Central

    Slater, Mel; Rovira, Aitor; Southern, Richard; Swapp, David; Zhang, Jian J.; Campbell, Claire; Levine, Mark

    2013-01-01

    Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation. PMID:23300991

  6. Bringing in the target audience in bystander social marketing materials for communities: suggestions for practitioners.

    PubMed

    Potter, Sharyn J; Stapleton, Jane G

    2011-06-01

    The Know Your Power™ social marketing campaign images model active bystander behaviors that target audience members can use in situations where sexual and relationship violence and stalking are occurring, have occurred, or have the potential to occur. In this practitioner note, we describe strategies that we have used to engage target audience members in the development of the social marketing campaign that we hope can be used by practitioners. We give examples from the development and evaluation of the Know Your Power(TM) social marketing campaign that used focus group and other types of feedback from the target audience to inform the direction of the campaign. PMID:21727157

  7. A tale of two cities: The role of neighborhood socioeconomic status in spatial clustering of bystander CPR in Austin and Houston☆

    PubMed Central

    Root, Elisabeth Dowling; Gonzales, Louis; Persse, David E.; Hinchey, Paul R.; McNally, Bryan; Sasson, Comilla

    2013-01-01

    Background Despite evidence to suggest significant spatial variation in out-of-hospital cardiac arrest (OHCA) and bystander cardiopulmonary resuscitation (BCPR) rates, geographic information systems (GIS) and spatial analysis have not been widely used to understand the reasons behind this variation. This study employs spatial statistics to identify the location and extent of clusters of bystander CPR in Houston and Travis County, TX. Methods Data were extracted from the Cardiac Arrest Registry to Enhance Survival for two U.S. sites –Austin-Travis County EMS and the Houston Fire Department – between October 1, 2006 and December 31, 2009. Hierarchical logistic regression models were used to assess the relationship between income and racial/ethnic composition of a neighborhood and BCPR for OHCA and to adjust expected counts of BCPR for spatial cluster analysis. The spatial scan statistic was used to find the geographic extent of clusters of high and low BCPR. Results Results indicate spatial clusters of lower than expected BCPR rates in Houston. Compared to BCPR rates in the rest of the community, there was a circular area of 4.2 km radius where BCPR rates were lower than expected (RR = 0.62; p < 0.0001 and RR = 0.55; p = 0.037) which persist when adjusted for individual-level patient characteristics (RR = 0.34; p = 0.027) and neighborhood-level race (RR = 0.34; p = 0.034) and household income (RR = 0.34; p = 0.046). We also find a spatial cluster of higher than expected BCPR in Austin. Compared to the rest of the community, there was a 23.8 km radius area where BCPR rates were higher than expected (RR = 1.75; p = 0.07) which disappears after controlling for individual-level characteristics. Conclusions A geographically targeted CPR training strategy which is tailored to individual and neighborhood population characteristics may be effective in reducing existing disparities in the provision of bystander CPR for out-of-hospital cardiac arrest. PMID:23318916

  8. The highly attenuated vaccinia virus strain modified virus Ankara induces apoptosis in melanoma cells and allows bystander dendritic cells to generate a potent anti-tumoral immunity

    PubMed Central

    Greiner, S; Humrich, J Y; Thuman, P; Sauter, B; Schuler, G; Jenne, L

    2006-01-01

    Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma in clinical trials for more than 40 years. Until now, mainly strains comparable to viral strains used for smallpox vaccination have been probed for anti-tumoral therapy. We have shown recently that the wild-type strain Western Reserve (WR) can interfere with crucial functions of monocyte-derived dendritic cells (DCs). Our aim was to examine whether viral immune evasion mechanisms might be responsible for the ineffectiveness of WR-based vaccination strategies and whether the highly attenuated strain modified virus Ankara (MVA) differs from WR with respect to its possible immunostimulatory capacity after intratumoral injection. Using in vitro experiments, we compared the effect of both strains on melanoma cells and on local bystander DCs. We found that both VV-strains infected melanoma cells efficiently and caused disintegration of the actin cytoskeleton, as shown by fluorescence microscopy. In addition, both VV-strains caused apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR underwent a complete viral replication cycle in melanoma cells. Bystander DCs were consecutively infected by newly generated WR virions and lost their capacity to induce allogeneic T cell proliferation. DCs in contact with MVA-infected melanoma cells retained their capacity to induce T cell proliferation. Immature DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of autologous CD8+ T cells by DCs that had phagocytosed MVA-infected, MelanA positive melanoma cells resulted in the induction of T cell clones specifically reactive against the model antigen MelanA as shown by enzyme-linked immunospot (ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type VV failed probably because of suppression of bystander DCs and consecutive suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain MVA facilitates the generation of

  9. Effect of correlated observation error on parameters, predictions, and uncertainty

    USGS Publications Warehouse

    Tiedeman, Claire R.; Green, Christopher T.

    2013-01-01

    Correlations among observation errors are typically omitted when calculating observation weights for model calibration by inverse methods. We explore the effects of omitting these correlations on estimates of parameters, predictions, and uncertainties. First, we develop a new analytical expression for the difference in parameter variance estimated with and without error correlations for a simple one-parameter two-observation inverse model. Results indicate that omitting error correlations from both the weight matrix and the variance calculation can either increase or decrease the parameter variance, depending on the values of error correlation (ρ) and the ratio of dimensionless scaled sensitivities (rdss). For small ρ, the difference in variance is always small, but for large ρ, the difference varies widely depending on the sign and magnitude of rdss. Next, we consider a groundwater reactive transport model of denitrification with four parameters and correlated geochemical observation errors that are computed by an error-propagation approach that is new for hydrogeologic studies. We compare parameter estimates, predictions, and uncertainties obtained with and without the error correlations. Omitting the correlations modestly to substantially changes parameter estimates, and causes both increases and decreases of parameter variances, consistent with the analytical expression. Differences in predictions for the models calibrated with and without error correlations can be greater than parameter differences when both are considered relative to their respective confidence intervals. These results indicate that including observation error correlations in weighting for nonlinear regression can have important effects on parameter estimates, predictions, and their respective uncertainties.

  10. Observation of the chiral magnetic effect in ZrTe₅

    SciTech Connect

    Li, Qiang; Kharzeev, Dmitri E.; Zhang, Cheng; Huang, Yuan; Pletikosic, I.; Fedorov, A. V.; Zhong, R. D.; Schneeloch, J. A.; Gu, G. D.; Valla, T.

    2015-02-08

    The chiral magnetic effect is the generation of electric current induced by chirality imbalance in the presence of magnetic field. It is a macroscopic manifestation of the quantum anomaly in relativistic field theory of chiral fermions (massless spin 1/2 particles with a definite projection of spin on momentum) – a dramatic phenomenon arising from a collective motion of particles and antiparticles in the Dirac sea. The recent discovery of Dirac semimetals with chiral quasi-particles opens a fascinating possibility to study this phenomenon in condensed matter experiments. Here we report on the first observation of chiral magnetic effect through the measurement of magneto-transport in zirconium pentatelluride, ZrTe₅. Our angle-resolved photoemission spectroscopy experiments show that this material’s electronic structure is consistent with a 3D Dirac semimetal. We observe a large negative magnetoresistance when magnetic field is parallel with the current. The measured quadratic field dependence of the magnetoconductance is a clear indication of the chiral magnetic effect. Furthermore, the observed phenomenon stems from the effective transmutation of Dirac semimetal into a Weyl semimetal induced by the parallel electric and magnetic fields that represent a topologically nontrivial gauge field background.

  11. Observation of the chiral magnetic effect in ZrTe₅

    DOE PAGESBeta

    Li, Qiang; Kharzeev, Dmitri E.; Zhang, Cheng; Huang, Yuan; Pletikosic, I.; Fedorov, A. V.; Zhong, R. D.; Schneeloch, J. A.; Gu, G. D.; Valla, T.

    2015-02-08

    The chiral magnetic effect is the generation of electric current induced by chirality imbalance in the presence of magnetic field. It is a macroscopic manifestation of the quantum anomaly in relativistic field theory of chiral fermions (massless spin 1/2 particles with a definite projection of spin on momentum) – a dramatic phenomenon arising from a collective motion of particles and antiparticles in the Dirac sea. The recent discovery of Dirac semimetals with chiral quasi-particles opens a fascinating possibility to study this phenomenon in condensed matter experiments. Here we report on the first observation of chiral magnetic effect through the measurementmore » of magneto-transport in zirconium pentatelluride, ZrTe₅. Our angle-resolved photoemission spectroscopy experiments show that this material’s electronic structure is consistent with a 3D Dirac semimetal. We observe a large negative magnetoresistance when magnetic field is parallel with the current. The measured quadratic field dependence of the magnetoconductance is a clear indication of the chiral magnetic effect. Furthermore, the observed phenomenon stems from the effective transmutation of Dirac semimetal into a Weyl semimetal induced by the parallel electric and magnetic fields that represent a topologically nontrivial gauge field background.« less

  12. Interference effects from observed movement in Parkinson’s disease

    PubMed Central

    Albert, Neil B.; Peiris, Yasmin; Cohen, Georgia; Miall, R. Chris; Praamstra, Peter

    2016-01-01

    Previous research has demonstrated that Parkinson’s disease patients have an increased susceptibility to response conflict. Here, we investigate whether Parkinson patients have a similar sensitivity to interference from observed movements. Ten patients and ten controls performed horizontal and vertical arm movements, while watching a video of a person performing similar movements or a moving dot. Movements were performed in the same plane (congruent) and orthogonal to the observed movement (incongruent). The off-axis variance of movements was our index of interference. While patients tended to exhibit more off-axis variability than controls, both groups demonstrated similar congruence effects, with greater variance in incongruent conditions. These results indicate that increased susceptibility to interference in Parkinson’s disease does not extend to interference from observed movements. PMID:20207605

  13. The relative biological effectiveness of out-of-field dose

    NASA Astrophysics Data System (ADS)

    Balderson, Michael; Koger, Brandon; Kirkby, Charles

    2016-01-01

    Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

  14. Confined space ventilation by shipyard welders: observed use and effectiveness.

    PubMed

    Pouzou, Jane G; Warner, Chris; Neitzel, Richard L; Croteau, Gerry A; Yost, Michael G; Seixas, Noah S

    2015-01-01

    Shipbuilding involves intensive welding activities within enclosed and confined spaces, and although ventilation is commonly used in the industry, its use and effectiveness has not been adequately documented. Workers engaged in welding in enclosed or confined spaces in two shipyards were observed for their use of ventilation and monitored for their exposure to particulate matter. The type of ventilation in use, its placement and face velocity, the movement of air within the space, and other ventilation-related parameters were recorded, along with task characteristics such as the type of welding, the welder's position, and the configuration of the space. Mechanical ventilation was present in about two-thirds of the 65 welding scenarios observed, with exhaust ventilation used predominantly in one shipyard and supply blowers predominantly in the other. Welders were observed working in apparent dead-spaces within the room in 53% of the cases, even where ventilation was in use. Respiratory protection was common in the two shipyards, observed in use in 77 and 100% of the cases. Welding method, the proximity of the welder's head to the fume, and air mixing were found to be significantly associated with the welder's exposure, while other characteristics of dilution ventilation did not produce appreciable differences in exposure level. These parameters associated with exposure reduction can be assessed subjectively and are thus good candidates for training on effective ventilation use during hot work in confined spaces. Ventilation used in confined space welding is often inadequate for controlling exposure to welding fume. PMID:25245587

  15. Confined space ventilation by shipyard welders: Observed use and effectiveness

    PubMed Central

    Pouzou, Jane; Warner, Chris; Neitzel, Rick; Croteau, Gerry; Yost, Michael; Seixas, Noah

    2016-01-01

    Shipbuilding involves intensive welding activities within enclosed and confined spaces and, although ventilation is commonly used in the industry, its use and effectiveness has not been adequately documented. Workers engaged in welding in enclosed or confined space in two shipyards were observed for their use of ventilation and monitored for their exposure to particulate matter. The type of ventilation in use, its placement and face velocity, the movement of air within the space, and other ventilation-related parameters were recorded, along with task characteristics such as the type of welding, the welder’s position, and the configuration of the space. Mechanical ventilation was present in about two thirds of the 65 welding scenarios observed, with exhaust ventilation used predominantly in one shipyard and supply blowers predominantly in the other. Welders were frequently observed working in apparent dead-spaces within the room, even where ventilation was in use. Respiratory protection was common in the two shipyards, observed in use in 77% and 100% of the cases. Welding method, the proximity of the welder’s head to the fume, and air mixing were found to be associated with the welder’s exposure, while other characteristics of the dilution ventilation did not produce appreciable differences in exposure level. These parameters associated with exposure reduction can be assessed subjectively and are thus good candidates for training on effective ventilation use during hot work in confined spaces. Ventilation used in confined space welding is often inadequate for controlling exposure to welding fume. PMID:25245587

  16. Helicity and the ALPHA-EFFECT:DYNAMO Theory and Observations

    NASA Astrophysics Data System (ADS)

    Kuzanyan, Kirill M.

    The best available tracers of the alpha-effect in the solar convection zone are current helicity and twist of the photospheric magnetic fields obtained by vector magnetographic observations. Here we present results of systematic studies of the current helicity and twist of averaged over a series of solar active regions. The data analysis enables us to reveal latitudinal dependence of the effect which is antisymmetric over the solar equator. Consideration of individual rotation rates of active regions versus the solar internal differential rotation law indicates that the radial structure of the alpha-effect is likely sign-changing. These properties are in agreement with theoretical estimates and numerical simulations of flows in the solar convection zone and model assumptions of dynamo theory. The fine structure of observational signatures of the alpha-effect indicates that the magnetic field generation mainly occurs near the bottom of the convection zone. We revealed some cyclic evolution of current helicity over the solar cycle that is in accord with dynamo models under certain parameter range. Thus knowledge on the spatially-temporal structure of signatures of the alpha-effect leads to further improvement of dynamo theory in description of the mechanism of generation of solar magnetic fields.

  17. Effects of coastal transport on larval patches: Models and observations

    NASA Astrophysics Data System (ADS)

    Tilburg, Charles E.; Houser, Letise T.; Steppe, Cecily N.; Garvine, Richard W.; Epifanio, Charles E.

    2006-03-01

    We used a combination of field observations and numerical modeling to examine the physical mechanisms responsible for the evolution and transport of patches of blue crab larvae in the mouth of Delaware Bay. The observations consisted of larval collections and surface salinity measurements taken along a moving spatial grid whose origin was determined by a satellite-tracked drifter. Examination of field observations revealed a slender larval patch that was aligned with salinity contours. Measurement of the salting rate of the larval patch indicated that the patch moved through the offshore edge of a buoyant plume due to wind-driven upwelling circulation. A numerical model that provided realistic simulations of the flow field at the mouth of Delaware Bay and the adjoining coastal ocean was used to examine the physical mechanisms responsible for the movement and evolution of the patch. We conducted a series of simulations in which we separately examined the effects of tides, buoyancy-driven flow, and wind-driven transport. Results showed that both tides and buoyancy-driven flow tend to elongate an initially square fluid element. Although winds alone have little effect on the shape of a patch, wind-driven flow can effectively move a patch through a complex flow field in which the deformation by tides and buoyancy-driven circulation can have significant effects. This study represents the first observation and analysis of a larval patch that remains intact while moving through the edge of a buoyant plume. It provides new insight into the shape of larval patches in Delaware Bay and any region with strong buoyancy- and tidally-driven flow, suggesting that typical larval patches may not be characterized by equal across- and alongshelf dimensions but instead tend to be slender shapes that are aligned with the flow field.

  18. Observation of an unusually large atomic parity-violation effect

    NASA Astrophysics Data System (ADS)

    Tsigutkin, Konstantin

    2010-03-01

    We report on observation of a large parity-violation effect in the atoms of ytterbium (Yb). This left-right asymmetry appears naturally in the Standard Model, and is associated with the exchange of a virtual heavy ``gauge" boson between subatomic particles. Eventually, parity violation has been observed and precisely measured by a number of groups in several different atoms, culminating in a 0.3% measurement in cesium (Cs) by Carl Wieman and co-workers at Boulder. The parity-violating amplitude of the 6x^2 ^1S0 -> 5d6s ^3D1 408-nm forbidden transition of ytterbium is found to be two orders of magnitude larger than in cesium. This is the largest atomic parity-violating amplitude yet observed. This also opens the way to future measurements of the parity violation effects for different Yb isotopes in order to test the effect of the neutron distributions within the nucleus and detect the so-called ``anapole moment" by comparing parity-violating amplitudes for various hyperfine components of the transition. So far, Cs is the only system where such a moment has been detected. Measurements of anapole moments are important for understanding the electroweak interactions within the nucleus which are hard to probe by other means.

  19. OBSERVATIONAL SELECTION EFFECTS AND THE M-{sigma} RELATION

    SciTech Connect

    Gueltekin, Kayhan; Richstone, Douglas O.; Tremaine, Scott; Loeb, Abraham

    2011-09-01

    We examine the possibility that the observed relation between black hole mass and host-galaxy stellar velocity dispersion (the M-{sigma} relation) is biased by an observational selection effect, the difficulty of detecting a black hole whose sphere of influence is smaller than the telescope resolution. In particular, we critically investigate recent claims that the M-{sigma} relation only represents the upper limit to a broad distribution of black hole masses in galaxies of a given velocity dispersion. We find that this hypothesis can be rejected at a high confidence level, at least for the early-type galaxies with relatively high velocity dispersions (median 268 km s{sup -1}) that comprise most of our sample. We also describe a general procedure for incorporating observational selection effects in estimates of the properties of the M-{sigma} relation. Applying this procedure we find results that are consistent with earlier estimates that did not account for selection effects, although with larger error bars. In particular, (1) the width of the M-{sigma} relation is not significantly increased, (2) the slope and normalization of the M-{sigma} relation are not significantly changed, and (3) most or all luminous early-type galaxies contain central black holes at zero redshift. Our results may not apply to late-type or small galaxies, which are not well represented in our sample.

  20. The role of gender, values, and culture in adolescent bystanders' strategies.

    PubMed

    Tamm, Anni; Tulviste, Tiia

    2015-02-01

    We examined the relationship between adolescent bystanders' strategies for intervening in the bullying-like situation and their gender, values, and cultural origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (M age = 13.02 years). They were shown a video of a bullying-like situation with a non-intervening adult bystander and asked to describe what they would do if they, instead of the adult, witnessed that situation. Only 10% said that they would not intervene. Girls were more likely than boys to suggest multiple actions. Adolescents who valued conformity were less likely to propose using physical aggression. Doing nothing was less likely suggested by those who placed more importance on conformity and less on power. Estonian adolescents were more likely than their Russian-Estonian peers to suggest finding out what is going on, and less likely to say that they would do nothing. The findings suggest that although most adolescents express willingness to help the victim, they might not actually know how to intervene. PMID:24919991

  1. Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.

    PubMed

    Suresh, Rahul; Chandrasekaran, Prabha; Sutterwala, Fayyaz S; Mosser, David M

    2016-05-01

    Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement-opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1β and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1β and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity. PMID:27006116

  2. The Effects of Lesson Study on Classroom Observations and Perceptions of Lesson Effectiveness

    ERIC Educational Resources Information Center

    Myers, Julia

    2012-01-01

    This study examined the effects of lesson study on participants' classroom observations and perceptions of lesson effectiveness, by investigating the focus of their observations during a mathematics lesson and their ratings of the lesson's effectiveness, both preceding and subsequent to the lesson study experience. Prior to the lesson study,…

  3. Bystanders' Reactions to Bullying: A Cross-Cultural Analysis of Personal Correlates among Italian and Singaporean Students

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Ang, Rebecca P.; Gini, Gianluca

    2012-01-01

    This study examined the role of attitudes against bullying and perceived peer pressure for intervention in explaining defending the victim and passive bystanding behavior in bullying. Participants were 1031 school-age children from two culturally diverse settings, namely Italy and Singapore, which are similar on several dimensions (e.g., quality…

  4. The Role of Individual Correlates and Class Norms in Defending and Passive Bystanding Behavior in Bullying: A Multilevel Analysis

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-01-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age = 10 years 1 month) and middle school (mean age = 13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g.,…

  5. How Students' Perceptions of the School Climate Influence Their Choice to Upstand, Bystand, or Join Perpetrators of Bullying

    ERIC Educational Resources Information Center

    Ferráns, Silvia Diazgranados; Selman, Robert L.

    2014-01-01

    The authors of this article, Silvia Diazgranados Ferráns and Robert Selman, use an emergent framework to explore how the rules of the school culture at different perceived school climates affect early adolescents' decisions to upstand, bystand, or join the perpetrators when they witness peer aggression and bullying. Through a grounded theory…

  6. The Emergence of New Paradigms in Student-University Relations: From In Loco Parentis to Bystander to Facilitator.

    ERIC Educational Resources Information Center

    Bickel, Robert D.; Lake, Peter F.

    1997-01-01

    University liability is in transition; its role changing from a parental/custodial "in loco parentis" model (and then a bystander role) to a new model of facilitator. The university enjoys a position of authority and respect, while exercising control more subtly than in the mid-1990s. At the same time, universities may be unable to claim the same…

  7. Atrial Fibrillation in Heart Failure: An Innocent Bystander?

    PubMed Central

    Khan, MA; Neyses, L; Mamas, MA

    2012-01-01

    Heart failure (HF) and atrial fibrillation (AF) frequently coexist and each complicates the course of the other. The purpose of this review is to analyse the prognostic impact of AF in patients with HF and assess whether there is an advantage in targeting therapies towards the maintenance of sinus rhythm (SR) in this cohort of patients. The presence of AF in patients with HF has been reported to be independently associated with an increase in mortality in many studies and this increased risk is observed in those with both preserved and impaired LV systolic function. The optimal strategy for targeting AF in patients with HF is unclear but recent randomised controlled studies indicate no significant prognostic advantage associated with a rhythm control strategy as compared to a rate control strategy. A number of small studies have investigated the role of both cardiac resynchronization therapy (CRT) and AF catheter ablation for the maintenance of / conversion to SR in patients with HF with initial promising results although larger randomised controlled studies will need to be performed to define the role of these modalities in the treatment of this cohort and whether preliminary benefits observed in these studies translate to improvements in longer term prognosis. Finally, there has been a focus on modifying the arrythmogenic atrial substrate and neurohormonal milieu by pharmacological means in order to prevent AF although it remains to be seen whether this approach proves to be efficacious with improvements in clinically relevant outcomes. PMID:22920477

  8. Sexual Violence Prevention through Bystander Education: An Experimental Evaluation

    ERIC Educational Resources Information Center

    Banyard, Victoria L.; Moynihan, Mary M.; Plante, Elizabethe G.

    2007-01-01

    The current study used an experimental design to evaluate a sexual violence prevention program based on a community of responsibility model that teaches women and men how to intervene safely and effectively in cases of sexual violence before, during, and after incidents with strangers, acquaintances, or friends. It approaches both women and men as…

  9. From Bystander to Ally: Transforming the District Human Resources Department

    ERIC Educational Resources Information Center

    Campbell, Christine; DeArmond, Michael; Schumwinger, Abigail

    2004-01-01

    Although policymakers and academics tend to overlook the behind-the-scenes role that district human resources (HR) departments play in education, the HR office's effect is far from small. HR departments determine whether qualified teacher candidates make it to the classroom, or slip through the cracks. They can help principals find teachers who…

  10. ASTRO-F/FIS observing simulation including detector effects

    NASA Astrophysics Data System (ADS)

    Jeong, W.; Pak, S.; Lee, H.; Nakagawa, T.; Kim, M.; Oh, S.; Kaneda, H.; Matsuura, S.; Patrashin, M.; Shibai, H.

    Based on the present hardware specifications and configurations of the ASTRO-F/FIS (Far-Infrared Surveyor), we are developing a software that simulates the observations with this instrument. Various kinds of detector effects affect the quality of the signal obtained from the detector. In order to correct the signal exactly, we need to analyze the characteristics of the detector and simulate various detector effects. In this presentation, we will show the simulated data sets based on the experimental data measured in the laboratory. Using the simulator, we will discuss the effects of cosmic-ray hitting, transient, crosstalk and non-uniformity of detectors, and propose an appropriate methods for the data reduction.

  11. Storm after-effects observed at Ushuaia and Kerguelen

    NASA Astrophysics Data System (ADS)

    Peres, M.

    1981-12-01

    D-region disturbances have been detected at mid-latitudes after intense magnetic storms by means of a wide range of radiowave signals. Two different mechanisms have been suggested to account for these storm 'after-effects': one implies precipitation of energetic electrons from the radiation belt; the other, transport of neutral constituents from the auroral zones. This paper presents observations of abnormal enhancements of ionospheric absorption arising after two major magnetic storms occurring in March and April 1976. The measurements were made at Ushuaia (54.8 deg S, L equals 1.7) and at Kerguelen (49.4 deg S, L equals 3.7). The former were obtained by means of the pulse reflection method (A1) at MF and the latter by the riometer technique. It is shown that electron precipitation can explain the effects observed at Kerguelen but not those at Ushuaia which also depart significantly from the 'winter anomaly' trend observed at that site. The abnormal ionization at Ushuaia is attributed to transport from the southern auroral zone.

  12. Finite Gyroradius Effects Observed in Pickup Oxygen Ions at Venus

    NASA Technical Reports Server (NTRS)

    Hartle, Richard E.; Intriligator, Devrie; Grebowsky, Joseph M.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    On the dayside of Venus, the hot oxygen corona extending above the ionopause is the principal source of pickup oxygen ions. The ions are born here and picked up by the ionosheath plasma as it is deflected around the planet. These pickup ions have been observed by the Orbiter Plasma Analyzer (OPA) throughout the Pioneer Venus Orbiter (PVO) mission. They were observed over a region extending from their dayside source to great distances downstream (about 10 Venus radii), in the solar wind wake, as PVO passed through apoapsis. Finite gyroradius effects in the velocity distribution of the oxygen pickup ions are expected in the source region because the gyroradius is several times larger than the scale height of the hot oxygen source. Such effects are also expected in those regions of the ionosheath where the scale lengths of the magnetic field and the ambient plasma velocity field are less than the pickup ion gyroradius. While explicitly accounting for the spatial distribution of the hot oxygen source, an analytic expression for the pickup oxygen ion velocity distribution is developed to study how it is affected by finite gyroradii. The analysis demonstrates that as the gyroradius increases by factors of three to six above the hot oxygen scale height, the peak of the pickup oxygen ion flux distribution decreases 25 to 50% below the maximum allowed speed, which is twice the speed of the ambient plasma times the sine of the angle between the magnetic field and the flow velocity. The pickup oxygen ion flux distribution observed by OPA is shown to follow this behavior in the source region. It is also shown that this result is consistent with the pickup ion distributions observed in the wake, downstream of the source, where the flux peaks are usually well below the maximum allowed speed.

  13. Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

    PubMed Central

    Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

    2015-01-01

    CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

  14. Experimental Observation of the Barnett Effect for Protons

    NASA Astrophysics Data System (ADS)

    Arabgol, Mohsen

    More than a century has passed since the experimental proof of the coupling between magnetization and rotation was found through the famous Einstein-de Hass experiment. Almost around the same time, Barnett experimentally demonstrated that the bulk rotation of an object leads to the partial alignment of the electronic magnetic moments widely known as the Barnett effect. Nevertheless, given the relatively small size of the magnetic moment of nucleons compared to electrons, the effect has not been experimentally detected at the nuclear level until the present day. The first and foremost objective of this study was to overcome this gap in experimental research. To measure the Nuclear Barnett Effect, we used a conventional low frequency NMR technique together with a high-speed spinner turbine. Our findings show that the observed nuclear magnetization due to rotation is consistent with the theoretical predictions; hence an experimental proof for the nuclear Barnett effect has been achieved. To demonstrate the validity of the results, a brief discussion on the effect of rotation on the intensity of the signal as well as an extensive analysis of the sources of error in low frequency NMR systems is provided.

  15. Chandra Observations of the Brightest Sunyaev-Zeldovich Effect Cluster

    NASA Astrophysics Data System (ADS)

    Hughes, John

    2011-09-01

    We propose deep Chandra observations of ACT-CL J0102-4915, the brightest Sunyaev-Zeldovich effect cluster discovered by the Atacama Cosmology Telescope and South Pole Telescope surveys. These surveys covered approximately 3000 square degrees and are essentially complete to high redshift. Our recent Chandra and VLT optical data reveal ACL-CL J0102-4915 to be undergoing a major merger. It is likely a high redshift (z=0.870) counterpart to the famous ``bullet'' cluster. New Chandra data will determine the properties of the merger shock and the HST/ACS data will provide a weak lensing mass map.

  16. Chandra Observations of the Brightest Sunyaev-Zeldovich Effect Cluster

    NASA Astrophysics Data System (ADS)

    Hughes, John

    2011-10-01

    We propose deep Chandra observations of ACT-CL J0102-4915, the brightest Sunyaev-Zeldovich effect cluster discovered by the Atacama Cosmology Telescope and South Pole Telescope surveys. These surveys covered approximately 3000 square degrees and are essentially complete to high redshift. Our recent Chandra and VLT optical data reveal ACL-CL J0102-4915 to be undergoing a major merger. It is likely a high redshift {z=0.870} counterpart to the famous A?A?bulletA?A? cluster. New Chandra data will determine the properties of the merger shock and the HST/ACS data will provide a weak lensing mass map.

  17. SUSY Spectrum Calculator Effects on Dark Matter Observables

    NASA Astrophysics Data System (ADS)

    Bergeron, Paul

    2016-03-01

    Due to questions like the dark matter and hierarchy problem, searches for physics beyond the Standard Model (SM) have not only moved beyond the simplest extensions but the LHC has offered the first tantalizing hints of a new particle at 750 GeV. But as we move into new regimes beyond the minimal extensions to the SM, we need to ask ourselves how accurate are our existing simulations of theory therein? In my talk I will explore the effects of different supersymmetric, spectrum calculators (e.g. ISAJET and SPheno) on predictions for dark matter and Higgs sector observables.

  18. Measuring effectiveness of drugs in observational databanks: promises and perils

    PubMed Central

    Krishnan, Eswar; Fries, James F

    2004-01-01

    Observational databanks have inherent strengths and shortcomings. As in randomized controlled trials, poor design of these databanks can either exaggerate or reduce estimates of drug effectiveness and can limit generalizability. This commentary highlights selected aspects of study design, data collection and statistical analysis that can help overcome many of these inadequacies. An international metaRegister and a formal mechanism for standardizing and sharing drug data could help improve the utility of databanks. Medical journals have a vital role in enforcing a quality checklist that improves reporting. PMID:15059263

  19. Observations of the first aerosol indirect effect in shallow cumuli

    SciTech Connect

    Berg, Larry K.; Berkowitz, Carl M.; Barnard, James C.; Senum, Gunar; Springston, Stephen R.

    2011-02-08

    Data from the Cumulus Humilis Aerosol Processing Study (CHAPS) are used to estimate the impact of both aerosol indirect effects and cloud dynamics on the microphysical and optical properties of shallow cumuli observed in the vicinity of Oklahoma City, Oklahoma. Not surprisingly, we find that the amount of light scattered by the clouds is dominated by their liquid water content (LWC), which in turn is driven by cloud dynamics. However, removing the effect of cloud dynamics by examining the scattering normalized by LWC shows a strong sensitivity of scattering to pollutant loading. These results suggest that even moderately sized cities, like Oklahoma City, can have a measureable impact on the optical properties of shallow cumuli.

  20. Experimental Observation of Negative Effective Gravity in Water Waves

    PubMed Central

    Hu, Xinhua; Yang, Jiong; Zi, Jian; Chan, C. T.; Ho, Kai-Ming

    2013-01-01

    The gravity of Earth is responsible for the formation of water waves and usually difficult to change. Although negative effective gravity was recently predicted theoretically in water waves, it has not yet been observed in experiments and remains a mathematical curiosity which is difficult to understand. Here we experimentally demonstrate that close to the resonant frequency of purposely-designed resonating units, negative effective gravity can occur for water waves passing through an array of resonators composing of bottom-mounted split tubes, resulting in the prohibition of water wave propagation. It is found that when negative gravity occurs, the averaged displacement of water surface in a unit cell of the array has a phase difference of π to that along the boundary of the unit cell, consistent with theoretical predictions. Our results provide a mechanism to block water waves and may find applications in wave energy conversion and coastal protection. PMID:23715132

  1. Waveguides for performing spectroscopy with confined effective observation volumes

    DOEpatents

    Levene, Michael J.; Korlach, Jonas; Turner, Stephen W.; Craighead, Harold G.; Webb, Watt W.

    2006-03-14

    The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

  2. First observation of muonic hyperfine effects in pure deuterium

    SciTech Connect

    Kammel, P.; Breunlich, W.H.; Cargnelli, M.; Mahler, H.G.; Zmeskal, J.; Bertl, W.H.; Petitjean, C.

    1983-11-01

    We discovered a strong hyperfine dependence of the resonant formation process of d..mu..d mesomolecules, while detecting neutrons from muon-catalyzed fusion in pure deuterium gas at 34 K. This new effect enabled us to observe directly transitions between hyperfine states of the ..mu..d atom for the first time and to determine an accurate experimental value for this transition rate. Our analysis demonstrates the importance of hyperfine effects for the quantitative understanding of the mechanism of resonant d..mu..d formation. Moreover, this experiment indicates that the resonant formation process is a powerful tool for a refined spectroscopy of d..mu..d bound states. Finally, the detailed knowledge about mesoatomic and mesomolecular processes obtained in this work provides valuable information for the analysis of experiments on the elementary muon-capture process in deuterium.

  3. Effective quantum gravity observables and locally covariant QFT

    NASA Astrophysics Data System (ADS)

    Rejzner, Kasia

    2016-03-01

    Perturbative algebraic quantum field theory (pAQFT) is a mathematically rigorous framework that allows to construct models of quantum field theories (QFTs) on a general class of Lorentzian manifolds. Recently, this idea has been applied also to perturbative quantum gravity (QG), treated as an effective theory. The difficulty was to find the right notion of observables that would in an appropriate sense be diffeomorphism invariant. In this paper, I will outline a general framework that allows to quantize theories with local symmetries (this includes infinitesimal diffeomorphism transformations) with the use of the Batalin-Vilkovisky (BV) formalism. This approach has been successfully applied to effective QG in a recent paper by Brunetti, Fredenhagen and myself. In the same paper, we also proved perturbative background independence of the quantized theory, which is going to be discussed in the present work as well.

  4. Effects of band-limited noise on human observer performance

    NASA Astrophysics Data System (ADS)

    Salem, Salem; Jacobs, Eddie; Moore, Richard; Hogervorst, Maarten; Bijl, Piet; Halford, Carl

    2007-04-01

    Perception tests establish the effects of spatially band-limited noise and blur on human observer performance. Previously, Bijl showed that the contrast threshold of a target image with spatially band-limited noise is a function of noise spatial frequency. He used the method of adjustment to find the contrast thresholds for each noise frequency band. A noise band exists in which the target contrast threshold reaches a peak relative to the threshold for higher- or lower-noise frequencies. Bijl also showed that the peak of this noise band shifts as high frequency information is removed from the target images. To further establish these results, we performed forced-choice experiments. First, a Night Vision and Electronics Sensors Directorate (NVESD) twelve (12)-target infrared tracked vehicle image set identification (ID) experiment, second, a bar-pattern resolving experiment, and third, a Triangle Orientation Discrimination (TOD) experiment. In all of the experiments, the test images were first spatially blurred, then spatially band-limited noise was added. The noise center spatial frequency was varied in half-octave increments over seven octaves. Observers were shown images of varying target-to-noise contrasts, and a contrast threshold was calculated for each spatial noise band. Finally, we compared the Targeting Task Performance (TTP) human observer model predictions for performance in the presence of spatially band-limited noise with these experimental results.

  5. Quantum tunneling observed without its characteristic large kinetic isotope effects

    PubMed Central

    Hama, Tetsuya; Ueta, Hirokazu; Kouchi, Akira; Watanabe, Naoki

    2015-01-01

    Classical transition-state theory is fundamental to describing chemical kinetics; however, quantum tunneling is also important in explaining the unexpectedly large reaction efficiencies observed in many chemical systems. Tunneling is often indicated by anomalously large kinetic isotope effects (KIEs), because a particle’s ability to tunnel decreases significantly with its increasing mass. Here we experimentally demonstrate that cold hydrogen (H) and deuterium (D) atoms can add to solid benzene by tunneling; however, the observed H/D KIE was very small (1–1.5) despite the large intrinsic H/D KIE of tunneling (≳100). This strong reduction is due to the chemical kinetics being controlled not by tunneling but by the surface diffusion of the H/D atoms, a process not greatly affected by the isotope type. Because tunneling need not be accompanied by a large KIE in surface and interfacial chemical systems, it might be overlooked in other systems such as aerosols or enzymes. Our results suggest that surface tunneling reactions on interstellar dust may contribute to the deuteration of interstellar aromatic and aliphatic hydrocarbons, which could represent a major source of the deuterium enrichment observed in carbonaceous meteorites and interplanetary dust particles. These findings could improve our understanding of interstellar physicochemical processes, including those during the formation of the solar system. PMID:26034285

  6. The Evershed Effect Observed with 0.2" Angular Resolution

    NASA Astrophysics Data System (ADS)

    Sánchez Almeida, J.; Márquez, I.; Bonet, J. A.; Domínguez Cerdeña, I.

    2007-04-01

    We present an analysis of the Evershed effect observed with a resolution of 0.2". Using the new Swedish 1 m Solar Telescope and its Littrow spectrograph, we scan a significant part of a sunspot penumbra. Spectra of the nonmagnetic line Fe I λ7090.4 allows us to measure Doppler shifts without magnetic contamination. The observed line profiles are asymmetric. The Doppler shift depends on the part of the line used for measuring, indicating that the velocity structure of penumbrae remains unresolved, even with our angular resolution. The observed line profiles are properly reproduced if two components with velocities between zero and several km s-1 coexist in the resolution elements. Using Doppler shifts at fixed line depths, we find a local correlation between upflows and bright structures and between downflows and dark structures. This association is not specific to the outer penumbra, but it also occurs in the inner penumbra. The existence of such a correlation was originally reported in 1969 by Beckers and Schröter, and it is suggestive of energy transport by convection in penumbrae.

  7. Adoptive Transfer of Dying Cells Causes Bystander-Induced Apoptosis

    PubMed Central

    Schwulst, Steven J.; Davis, Christopher G.; Coopersmith, Craig M.; Hotchkiss, Richard S.

    2009-01-01

    The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type has been reported to protect against cell death in neighboring non-Bcl-2 overexpressing cell types. The mechanism of this “trans” protection has been speculated to be secondary to the release of a cytoprotective factor by Bcl-2 overexpressing cells. We employed a series of adoptive transfer experiments in which lymphocytes that overexpress Bcl-2 were administered to either wild type mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or absence of the putative protective factor. We were unable to demonstrate “trans” protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p≤0.05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e. a “trans” destructive effect. PMID:17194455

  8. Adoptive transfer of dying cells causes bystander-induced apoptosis.

    PubMed

    Schwulst, Steven J; Davis, Christopher G; Coopersmith, Craig M; Hotchkiss, Richard S

    2007-02-16

    The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type has been reported to protect against cell death in neighboring non-Bcl-2 overexpressing cell types. The mechanism of this "trans" protection has been speculated to be secondary to the release of a cytoprotective factor by Bcl-2 overexpressing cells. We employed a series of adoptive transfer experiments in which lymphocytes that overexpress Bcl-2 were administered to either wild type mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or absence of the putative protective factor. We were unable to demonstrate "trans" protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p < or= 0.05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e., a "trans" destructive effect. PMID:17194455

  9. CORAL: model for no observed adverse effect level (NOAEL).

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Pizzo, Fabiola; Lombardo, Anna; Gadaleta, Domenico; Benfenati, Emilio

    2015-08-01

    The in vivo repeated dose toxicity (RDT) test is intended to provide information on the possible risk caused by repeated exposure to a substance over a limited period of time. The measure of the RDT is the no observed adverse effect level (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint indicates the safety level for a substance. The need to replace in vivo tests, as required by some European Regulations (registration, evaluation authorization and restriction of chemicals) is leading to the searching for reliable alternative methods such as quantitative structure-activity relationships (QSAR). Considering the complexity of the RDT endpoint, for which data quality is limited and depends anyway on the study design, the development of QSAR for this endpoint is an attractive task. Starting from a dataset of 140 organic compounds with NOAEL values related to oral short term toxicity in rats, we developed a QSAR model based on optimal descriptors calculated with simplified molecular input-line entry systems and the graph of atomic orbitals by the Monte Carlo method, using CORAL software. Three different splits into the training, calibration, and validation sets are studied. The mechanistic interpretation of these models in terms of molecular fragment with positive or negative contributions to the endpoint is discussed. The probabilistic definition for the domain of applicability is suggested. PMID:25850638

  10. Chiral Colloidal Molecules And Observation of The Propeller Effect

    PubMed Central

    2013-01-01

    Chiral molecules play an important role in biological and chemical processes, but physical effects due to their symmetry-breaking are generally weak. Several physical chiral separation schemes which could potentially be useful, including the propeller effect, have therefore not yet been demonstrated at the molecular scale. However, it has been proposed that complex nonspherical colloidal particles could act as “colloidal molecules” in mesoscopic model systems to permit the visualization of molecular phenomena that are otherwise difficult to observe. Unfortunately, it is difficult to synthesize such colloids because surface minimization generally favors the growth of symmetric particles. Here we demonstrate the production of large numbers of complex colloids with glancing angle physical vapor deposition. We use chiral colloids to demonstrate the Baranova and Zel’dovich (BaranovaN. B.Zel’dovichB. Y.Chem. Phys. Lett.1978, 57, 435) propeller effect: the separation of a racemic mixture by application of a rotating field that couples to the dipole moment of the enantiomers and screw propels them in opposite directions. The handedness of the colloidal suspensions is monitored with circular differential light scattering. An exact solution for the colloid’s propulsion is derived, and comparisons between the colloidal system and the corresponding effect at the molecular scale are made. PMID:23883328

  11. CNODES: the Canadian Network for Observational Drug Effect Studies.

    PubMed

    Suissa, Samy; Henry, David; Caetano, Patricia; Dormuth, Colin R; Ernst, Pierre; Hemmelgarn, Brenda; Lelorier, Jacques; Levy, Adrian; Martens, Patricia J; Paterson, J Michael; Platt, Robert W; Sketris, Ingrid; Teare, Gary

    2012-01-01

    Although administrative health care databases have long been used to evaluate adverse drug effects, responses to drug safety signals have been slow and uncoordinated. We describe the establishment of the Canadian Network for Observational Drug Effect Studies (CNODES), a collaborating centre of the Drug Safety and Effectiveness Network (DSEN). CNODES is a distributed network of investigators and linked databases in British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia. Principles of operation are as follows: (1) research questions are prioritized by the coordinating office of DSEN; (2) the linked data stay within the provinces; (3) for each question, a study team formulates a detailed protocol enabling consistent analyses in each province; (4) analyses are "blind" to results obtained elsewhere; (5) protocol deviations are permitted for technical reasons only; (6) analyses using multivariable methods are lodged centrally with a methods team, which is responsible for combining the results to provide a summary estimate of effect. These procedures are designed to achieve high internal validity of risk estimates and to eliminate the possibility of selective reporting of analyses or outcomes. The value of a coordinated multi-provincial approach is illustrated by projects studying acute renal injury with high-potency statins, community-acquired pneumonia with proton pump inhibitors, and hyperglycemic emergencies with antipsychotic drugs. CNODES is an academically based distributed network of Canadian researchers and data centres with a commitment to rapid and sophisticated analysis of emerging drug safety signals in study populations totalling over 40 million. PMID:23687528

  12. Low Dose Studies with Focused X-Rays in cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    SciTech Connect

    Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

    2002-12-14

    the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  13. Low Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    SciTech Connect

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

    of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  14. The Effect of Observation Length and Presentation Order on the Reliability and Validity of an Observational Measure of Teaching Quality

    ERIC Educational Resources Information Center

    Mashburn, Andrew J.; Meyer, J. Patrick; Allen, Joseph P.; Pianta, Robert C.

    2014-01-01

    Observational methods are increasingly being used in classrooms to evaluate the quality of teaching. Operational procedures for observing teachers are somewhat arbitrary in existing measures and vary across different instruments. To study the effect of different observation procedures on score reliability and validity, we conducted an experimental…

  15. Live Video Classroom Observation: An Effective Approach to Reducing Reactivity in Collecting Observational Information for Teacher Professional Development

    ERIC Educational Resources Information Center

    Liang, Jiwen

    2015-01-01

    This paper examines the significance of live video classroom observations of teaching practice to reduce reactivity (the observer effect) so as to obtain more credible observational information for teacher professional development in a secondary school in the largest city in southern China. Although much has been discussed regarding the use of…

  16. A patient with commotio cordis successfully resuscitated by bystander cardiopulmonary resuscitation and automated external defibrillator.

    PubMed

    Ngai, K Y; Chan, H Y; Ng, F

    2010-10-01

    Sudden deaths of children and adolescents during competitive sports are usually due to congenital heart diseases. Ventricular fibrillation, however, may also occur in individuals with no underlying cardiac disease who have sustained a low-impact chest wall blow. This phenomenon is described as commotio cordis, and the overall survival rate is poor. Successful resuscitation can be achieved by prompt cardiopulmonary resuscitation and early defibrillation. We report a teenager who sustained a chest wall blow that resulted in a cardiac arrest during a rugby competition. Cardiopulmonary resuscitation was given by bystanders. The ambulance crew arrived with an automated external defibrillator. Ventricular fibrillation was detected and responded to defibrillation. Subsequent investigations including imaging and electrophysiological studies did not reveal any cardiac or brain abnormality, and the patient recovered well neurologically. Accessible cardiopulmonary resuscitation-trained personnel and automated external defibrillators should be present at all organised sporting events. PMID:20890008

  17. The bone marrow stroma in hematological neoplasms—a guilty bystander

    PubMed Central

    Tripodo, Claudio; Sangaletti, Sabina; Piccaluga, Pier P.; Prakash, Sonam; Franco, Giovanni; Borrello, Ivan; Orazi, Attilio; Colombo, Mario P.; Pileri, Stefano A.

    2013-01-01

    In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma. PMID:21448151

  18. Re-Evaluating Sexual Violence Prevention Through Bystander Education: A Latent Growth Curve Approach.

    PubMed

    Shaw, Jessica; Janulis, Patrick

    2016-10-01

    Recently, there has been a call for more advanced analytic techniques in violence against women research, particularly in community interventions that use longitudinal designs. The current study re-evaluates experimental evaluation data from a sexual violence bystander intervention program. Using an exploratory latent growth curve approach, we were able to model the longitudinal growth trajectories of individual participants over the course of the entire study. Although the results largely confirm the original evaluation findings, the latent growth curve approach better fits the demands of "messy" data (e.g., missing data, varying number of time points per participant, and unequal time spacing within and between participants) that are frequently obtained during a community-based intervention. The benefits of modern statistical techniques to practitioners and researchers in the field of sexual violence prevention, and violence against women more generally, are further discussed. PMID:25888503

  19. The role of individual and collective moral disengagement in peer aggression and bystanding: a multilevel analysis.

    PubMed

    Gini, Gianluca; Pozzoli, Tiziana; Bussey, Kay

    2015-04-01

    This study investigates the relationships between individual and collective moral disengagement and aggression-related behaviors (peer aggression, defending, and passive bystanding) among 918 adolescents (55.8% boys; M age = 14.1 years, SD = 1.1). Hierarchical linear modeling showed that, at the individual level, aggressive behavior was significantly explained by both individual moral disengagement and student perceived collective moral disengagement, which was also positively associated with defending. Student perceived collective moral disengagement moderated the link between individual moral disengagement and peer aggression. At the class level, classroom collective moral disengagement explained between-class variability in all the three aggression-related behaviors. These results extend previous research by demonstrating the role of collective moral disengagement at the individual and the class levels and have potential implications for interventions. PMID:25123080

  20. Photoelectric effect from observer's mathematics point of view

    NASA Astrophysics Data System (ADS)

    Khots, Boris; Khots, Dmitriy

    2014-12-01

    When we consider and analyze physical events with the purpose of creating corresponding models we often assume that the mathematical apparatus used in modeling is infallible. In particular, this relates to the use of infinity in various aspects and the use of Newton's definition of a limit in analysis. We believe that is where the main problem lies in contemporary study of nature. This work considers Physical aspects in a setting of arithmetic, algebra, geometry, analysis, topology provided by Observer's Mathematics (see www.mathrelativity.com). Certain results and communications pertaining to solution of these problems are provided. In particular, we prove the following Theorems, which give Observer's Mathematics point of view on Einstein photoelectric effect theory and Lamb-Scully and Hanbury-Brown-Twiss experiments: Theorem 1. There are some values of light intensity where anticorrelation parameter A ∈ [0,1). Theorem 2. There are some values of light intensity where anticorrelation parameter A = 1. Theorem 3. There are some values of light intensity where anticorrelation parameter A > 1.

  1. Pinatubo eruption winter climate effects: Model versus observations

    NASA Technical Reports Server (NTRS)

    Graf, HANS-F.; Kirchner, Ingo; Schult, Ingrid; Robock, Alan

    1992-01-01

    Large volcanic eruptions, in addition to the well-known effect of producing global cooling for a year or two, have been observed to produce shorter-term responses in the climate system involving non-linear dynamical processes. In this paper, we use the ECHAM2 general circulation model forced with stratospheric aerosols to test some of these ideas. Run in a perpetual-January mode, with tropical stratospheric heating from the volcanic aerosols typical of the 1982 El Chichon eruption or the 1991 Pinatubo eruption, we find a dynamical response with an increased polar night jet in the Northern Hemisphere (NH) and stronger zonal winds which extended down into the troposphere. The Azores High shifts northward with increased tropospheric westerlies at 60N and increased easterlies at 30N. Surface temperatures are higher both in northern Eurasia and North America, in agreement with observations for the NH winters or 1982-83 and 1991-92 as well as the winters following the other 10 largest volcanic eruptions since 1883.

  2. Atmospheric Effects on Cosmic Ray Air Showers Observed with HAWC

    NASA Astrophysics Data System (ADS)

    Young, Steven

    2014-01-01

    The High Altitude Water Cherenkov Gamma Ray detector (HAWC), currently under construction on the Sierra Negra volcano near Puebla, Mexico, can be used to study solar physics with its scaler data acquisition system. Increases in the scaler rates are used to observe GeV cosmic rays from solar flares while decreases in the rates show the heliospheric disturbances associated with coronal mass ejections. However, weather conditions and height-dependent state variables such as pressure and temperature affect the production of extensive particle air showers that can be detected by the scaler system. To see if these atmospheric effects can be removed, we obtained local weather data from the Global Data Assimilation System (GDAS) and the local weather station at HAWC. The scaler pulse rates were then correlated to the pressure and temperature. We present data from a Forbush decrease observed by HAWC following a significant coronal mass ejection in April 2013, and describe our efforts to remove atmospheric variations from the scaler counts. This work was partially supported by the National Science Foundation’s REU program through NSF Award AST-1004881 to the University of Wisconsin-Madison.

  3. Bullying Bystanders

    ERIC Educational Resources Information Center

    Jeffrey, Linda R.

    2004-01-01

    Bullies like an audience, and bullying is often a public interaction in which there are perceived winners and losers. While some victims are targeted because of a perceived vulnerability or difference, it is also the case that anyone can become a victim of bullying. As such, students intuitively weigh their own chances of becoming victims and…

  4. Ramadan and sport: minimizing effects upon the observant athlete.

    PubMed

    Shephard, Roy J

    2013-12-01

    exercise is impaired, but aerobic power and muscular strength show little change during Ramadan. Ratings of fatigue are increased, and vigilance and reaction times are impaired, particularly during the afternoon. Medical issues during Ramadan are few. Athletes with diabetes mellitus should seek a medical exemption from fasting, and prescribed drug schedules should be carefully maintained. There is no major increase of injury rates, but competitors may have difficulty in producing urine for doping controls. Logical measures to minimize the effects of Ramadan include the optimization of mood state, maintenance of training, minimization of sleep loss, appropriate adjustments of diet, and the monitoring of competitors for chronic dehydration. Future research should concentrate on the changes observed in top athletes, particularly women, with data collected in the late afternoon after a known period of fasting in a well defined environment. It will be important to ensure that the lifestyle of those studied has been optimized. Implications of chronic dehydration for doping control also merit further investigation. Current data suggest that the impact of Ramadan upon athletic performance is small relative to the precision of test procedures, although it may be sufficient to cause a loss of medals. Negative effects vary widely with the type of sport, the season when fasting is observed, the local culture and the discipline exercised by the athlete. PMID:23888431

  5. Engaging Active Bystanders in Mass Casualty Events and Other Life-Threatening Emergencies: A Pilot Training Course Demonstration.

    PubMed

    Smith, Tracey O; Baker, Susan D; Roberts, Kathryn; Payne, Skip A

    2016-04-01

    Emerging research indicates the critical role members of the public can play in saving lives and reducing morbidity at the scene in the immediate aftermath of a disaster. It is anticipated that with training, more members of the public will be ready and able to assist should they be present at mass casualty events or other circumstances in which there are serious injuries or potential loss of life. This article describes a training course developed by multiple federal and nonfederal partners aimed at preparing the public to become "active bystanders" followed by a pilot demonstration project conducted by Medical Reserve Corps Units. The outcomes of the project indicated that the training was comprehensive and appropriate for members of the public with little or no first aid knowledge. National availability of the "Becoming an Active Bystander" training course is currently being planned. PMID:26841861

  6. The role of individual correlates and class norms in defending and passive bystanding behavior in bullying: a multilevel analysis.

    PubMed

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-11-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age=10 years 1 month) and middle school (mean age=13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g., provictim attitudes and perceived peer pressure for intervention) and class characteristics (e.g., class provictim attitudes, peer injunctive norms, and descriptive norms) help explain defending and passive bystanding behavior in bullying. These results significantly expand previous findings in this field, by demonstrating the need for a social-ecological approach to the study of the different aspects of bullying. Implications for antibullying programs are discussed. PMID:22880944

  7. Direct observation of resonance effects in laser cluster interactions

    SciTech Connect

    Zweiback, J

    1999-06-01

    Time resolved dynamics of high intensity laser interactions with atomic clusters have been studied with both theoretical analysis and experiment. A short-pulse Ti:sapphire laser system, which could produce 50 mJ of energy in a 50 fs pulse, was built to perform these experiments. The laser used a novel single grating stretcher and was pumped, in part, by a custom Nd:YLF laser system, including 19 mm Nd:YLF amplifiers. It was found that there is an optimal pulse width to maximize absorption for a given cluster size. This optimal pulse width ranged from 400 fs for 85 A radius xenon clusters to 1.2 ps for 205 {angstrom} radius xenon clusters. Using a pump-probe configuration, the absorption of the probe radiation was observed to reach a maximum for a particular time delay between pump and probe, dependent on the cluster size. The delay for peak absorption was 800, 1400, and 2100 fs for 85 {angstrom}, 130 {angstrom}, and 170 {angstrom} radius xenon clusters respectively. Model calculations suggest that these effects are due to resonant heating of the spherical plasma in agreement with the hydrodynamic interpretation of cluster interactions. While this simple hydrodynamic code produces reasonable agreement with data, it does not include bulk plasma or non-linear propagation effects and is limited to the regime where resonant behavior dominates. We also measured the scattered laser light from the laser-cluster interaction. Similar to the absorption measurements, there is an optimal pulse width which maximizes the scattered signal. This pulse width is larger than the optimal pulse width for absorption. This disagrees with model calculations which show both pulse widths being similar. Further experiments measuring the scattered light in a pump-probe configuration should help to resolve this disagreement.

  8. MESSENGER Observations of Reconnection and Its Effects on Mercury's Magnetosphere

    NASA Technical Reports Server (NTRS)

    Slavin, James A.; Anderson, Brian J.; Baker, Daniel N.; Benna, Mehdi; Boardsen, Scott A.; Gloeckler, George; Gold, Robert E.; Ho, George C.; Imber, Suzanne M.; Korth, Haje; Krimigis, Stamatios M.; McNutt, Ralph L., Jr.; Nittler, Larry R.; Raines, Jim M.; Sarantos, Menelaos; Schriver, David; Solomon, Sean C.; Starr, Richard D.; Travnicek, Pavel; Zurbuchen, Thomas H.

    2010-01-01

    During MESSENGER's second and third flybys of Mercury on October 6, 2008 and September 29, 2009, respectively, southward interplanetary magnetic fields produced very intense reconnection signatures in the dayside and nightside magnetosphere and very different systemlevel responses. The IMF during the second flyby was continuously southward and the magnetosphere appeared very active with very large magnetic fields normal to the magnetopause and the generation of flux transfer events at the magnetopause and plasmoids in the tail current sheet every 30 s to 90 s. However, the strength and direction of the tail magnetic field was very stable. In contrast the third flyby experienced a variable IMF with it varying from north to south on timescales of minutes. Although the MESSENGER measurements were limited this time to the nightside magnetosphere, numerous examples of plasmoid release in the tail were detected, but they were not periodic. Rather, plasmoid release was highly correlated with the four large enhancements of the tail magnetic field (i.e. by factors > 2) with durations of approx. 2 - 3 min. The increased flaring of the magnetic field during these intervals indicates that the enhancements were caused by loading of the tail with magnetic flux transferred from the dayside magnetosphere. New analyses of the second and third flyby observations of reconnection and its system-level effects will be presented. The results will be examined in light of what is known about the response of the Earth's magnetosphere to variable versus steady southward IMF.

  9. Observation of room-temperature skyrmion Hall effect

    NASA Astrophysics Data System (ADS)

    Jiang, W.; Zhang, X.; Upadhyaya, P.; Zhang, W.; Yu, G.; Jungfleisch, M.; Fradin, F.; Pearson, J.; Tserkovnyak, Y.; Wang, K.; Heinonen, O.; Zhou, Y.; Te Velthuis, Suzanne; Hoffmann, A.

    The realization of room-temperature magnetic skyrmions is key to enabling the implementation of skyrmion-based spintronics. In this work, we present the efficient conversion of chiral stripe domains into Néel skyrmions through a geometrical constriction patterned in a Ta/CoFeB/TaOx trilayer film at room temperature. This is enabled by an interfacial Dzyaloshinskii-Moriya interaction, and laterally divergent current-induced spin-orbit torques. We further show the generation of magnetic skyrmions solely by the divergent spin-orbit torques through a nonmagnetic point contact. By increasing the current density, we observe the skyrmion Hall effect - that is the accumulation of skyrmions at one side of the device. The related Hall angle for skyrmion motion is also revealed under an ac driving current. Financial support for the work at Argonne came from Department of Energy, Office of Science, Basic Energy Science, Materials Sciences and Engineering Division, work at UCLA was supported by TANMS.

  10. An Observational Detection of the Bridge Effect of Void Filaments

    NASA Astrophysics Data System (ADS)

    Shim, Junsup; Lee, Jounghun; Hoyle, Fiona

    2015-12-01

    The bridge effect of void filaments is a phrase coined by Park & Lee to explain the correlations found in a numerical experiment between the luminosity of the void galaxies and the degree of straightness of their host filaments. Their numerical finding implies that a straight void filament provides a narrow channel for the efficient transportation of gas and matter particles from the surroundings into void galaxies. Analyzing the Sloan void catalog constructed by Pan et al., we identify the filamentary structures in void regions and determine the specific size of each void filament as a measure of its straightness. To avoid possible spurious signals caused by Malmquist bias, we consider only those void filaments whose redshifts are in the range 0≤slant z≤slant 0.02 and find a clear tendency that the void galaxies located in the straighter filaments are on average more luminous, which is in qualitative agreement with the numerical prediction. It is also shown that the strength of correlation increases with the number of member galaxies in the void filaments, which can be understood physically on the grounds that the more stretched filaments can connect the dense surroundings even to galaxies located deep in the central parts of the voids. This observational evidence may provide a key clue to the puzzling issue of why the void galaxies have higher specific star formation rates and bluer colors than their wall counterparts.

  11. Space environmental effects observed on the Hubble Space Telescope

    NASA Technical Reports Server (NTRS)

    Edelman, Joel E.; Mason, James B.

    1995-01-01

    The Hubble Space Telescope (HST) Repair Mission of December, 1993, was first and foremost a mission to improve the performance of the observatory. But for a specialized segment of the aerospace industry, the primary interest is in the return to Earth of numerous pieces of the HST hardware, pieces which have been replaced, repaired, improved, or superseded. The returned hardware is of interest because of the information it potentially carries about the effects of exposure to the space environment for three and a half years. Like the LDEF retrieval mission four years ago, the HST repair mission is of interest to many engineering disciplines, including all of the disciplines represented by the LDEF Special Investigation Groups (SIG's). There is particular interest in the evaluation of specific materials and systems in the returned components. Some coated surfaces have been processed with materials which are newer and still in use by, or under consideration for, other spacecraft in a variety of stages of development. Several of the systems are being returned because a specific failure or anomaly has been observed and thus there is, at the outset, a specific investigative trail that needs to be followed. These systems are much more complex than those flown on LDEF and, in two instances, comprised state-of-the-art science instruments. Further, the parts used in these systems generally were characterized more rigorously prior to flight than were those in the LDEF systems, and thus post flight testing may yield more significant results.

  12. Space environmental effects observed on the Hubble Space Telescope

    SciTech Connect

    Edelman, J.E.; Mason, J.B.

    1995-02-01

    The Hubble Space Telescope (HST) Repair Mission of December, 1993, was first and foremost a mission to improve the performance of the observatory. But for a specialized segment of the aerospace industry, the primary interest is in the return to Earth of numerous pieces of the HST hardware, pieces which have been replaced, repaired, improved, or superseded. The returned hardware is of interest because of the information it potentially carries about the effects of exposure to the space environment for three and a half years. Like the LDEF retrieval mission four years ago, the HST repair mission is of interest to many engineering disciplines, including all of the disciplines represented by the LDEF Special Investigation Groups (SIG`s). There is particular interest in the evaluation of specific materials and systems in the returned components. Some coated surfaces have been processed with materials which are newer and still in use by, or under consideration for, other spacecraft in a variety of stages of development. Several of the systems are being returned because a specific failure or anomaly has been observed and thus there is, at the outset, a specific investigative trail that needs to be followed. These systems are much more complex than those flown on LDEF and, in two instances, comprised state-of-the-art science instruments. Further, the parts used in these systems generally were characterized more rigorously prior to flight than were those in the LDEF systems, and thus post flight testing may yield more significant results.

  13. A Functional Analysis on the Effects of an Observational Intervention Using a Peer-Yoked Contingency Game Board on the Induction of Observational Performance, Observational Acquisition, and Naming

    ERIC Educational Resources Information Center

    Gold, Lisa Danielle

    2013-01-01

    The purpose of this study was to test the effects of a peer-yoked contingency on the induction of observational performance, observational acquisition, and the Naming capability. In Experiment I, three male kindergarten and first grade students diagnosed with disabilities were selected as target participants because they had the listener component…

  14. Effect of Observation Mode on Measures of Secondary Mathematics Teaching

    ERIC Educational Resources Information Center

    Casabianca, Jodi M.; McCaffrey, Daniel F.; Gitomer, Drew H.; Bell, Courtney A.; Hamre, Bridget K.; Pianta, Robert C.

    2013-01-01

    Classroom observation of teachers is a significant part of educational measurement; measurements of teacher practice are being used in teacher evaluation systems across the country. This research investigated whether observations made live in the classroom and from video recording of the same lessons yielded similar inferences about teaching.…

  15. PAS-1, a protein affinity purified from Ascaris suum worms, maintains the ability to modulate the immune response to a bystander antigen.

    PubMed

    Oshiro, Telma M; Enobe, Cristina S; Araújo, Cláudia A; Macedo, Mahasti S; Macedo-Soares, Maria Fernanda

    2006-04-01

    Helminth infections and parasite components have potent immunomodulatory effects on a host's immune system. In the present study, we investigated the effect of PAS-1, a protein component of Ascaris suum adult worms recognized by a monoclonal antibody (MAIP-1), on humoral and cell-mediated responses to a bystander antigen (ovalbumin [OVA]). MAIP-1 recognized only one of the three polypeptide chains of PAS-1, but neutralized the suppressive effect of the whole worm extract on OVA-specific antibody production. PAS-1 inhibited antibody production against a T-cell-dependent, but not a T-cell-independent, antigen in a dose-dependent way. IgM, IgG1, IgG2b, and also IgE and anaphylactic IgG1 levels were downregulated. In addition, PAS-1 inhibited OVA-specific delayed type hypersensitivity reactions in the footpad of mice, showing a potent immunosuppressive activity on both Th1 and Th2 responses that seems to be mediated by the induction of large amounts of IL-10 and IL-4. Indeed, PAS-1-specific spleen cells secreted sevenfold more IL-10 and threefold more IL-4 than OVA-specific cells in response to in vitro restimulation with the respective antigens. In conclusion, we showed that PAS-1, a single protein component from A. suum, maintains all its immunosuppressive properties. PMID:16519731

  16. Effect of video self-observations vs. observations of others on insight in psychotic disorders.

    PubMed

    David, Anthony S; Chis Ster, Irina; Zavarei, Hooman

    2012-04-01

    Improving insight in patients with schizophrenia and related disorders is a worthwhile goal. Previous work has suggested that patients' insight may improve if they see videos of themselves taken when ill. Our aim was to test the hypothesis that schizophrenia patients improve their insight after viewing videos of themselves when unwell more so than after viewing an actor. Forty patients admitted with an acute psychotic disorder underwent a videotaped recording of a clinical interview. The patients were then randomized to viewing this or a "control" video of a same-sex actor displaying psychotic symptoms approximately 3 weeks later. Insight, psychopathology, and mood were assessed before and 24 to 48 hours after viewing the videos. All participants showed general improvement across all measures. There was a trend for scores on the Schedule for the Assessment of Insight to improve more in those who viewed themselves when ill, but there were no clear statistically significant differences between the "self" and "other" video groups. In conclusion, video self-confrontation seems to be a safe and potentially effective means of enhancing insight, but evidence for a specific effect is lacking. PMID:22456591

  17. Anthropic shadow: observation selection effects and human extinction risks.

    PubMed

    Cirković, Milan M; Sandberg, Anders; Bostrom, Nick

    2010-10-01

    We describe a significant practical consequence of taking anthropic biases into account in deriving predictions for rare stochastic catastrophic events. The risks associated with catastrophes such as asteroidal/cometary impacts, supervolcanic episodes, and explosions of supernovae/gamma-ray bursts are based on their observed frequencies. As a result, the frequencies of catastrophes that destroy or are otherwise incompatible with the existence of observers are systematically underestimated. We describe the consequences of this anthropic bias for estimation of catastrophic risks, and suggest some directions for future work. PMID:20626690

  18. Observation of a Large Atomic Parity Violation Effect in Ytterbium

    SciTech Connect

    Tsigutkin, K.; Dounas-Frazer, D.; Family, A.; Stalnaker, J. E.; Yashchuk, V. V.; Budker, D.

    2009-08-14

    Atomic parity violation has been observed in the 6s{sup 2} {sup 1}S{sub 0}->5d6s {sup 3}D{sub 1} 408-nm forbidden transition of ytterbium. The parity-violating amplitude is found to be 2 orders of magnitude larger than in cesium, where the most precise experiments to date have been performed. This is in accordance with theoretical predictions and constitutes the largest atomic parity-violating amplitude yet observed. This also opens the way to future measurements of neutron distributions and anapole moments by comparing parity-violating amplitudes for various isotopes and hyperfine components of the transition.

  19. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

    PubMed

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Case, C Patrick

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  20. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells

    PubMed Central

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Patrick Case, C

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  1. The not-so innocent bystander: The microenvironment as a therapeutic target in cancer

    SciTech Connect

    Erickson, Anna C.; Barcellos-Hoff, Mary Helen

    2003-06-19

    The microenvironment in which cancer arises is often regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of the tumour. However, a major function of the microenvironment is to suppress cancer, and its disruption is required for the establishment of cancer. In addition, tumour cells can further distort the microenvironment to promote growth, recruit non-malignant cells that provide physiological resources, and facilitate invasion. In this review, the authors discuss the contribution of the microenvironment, i.e., the stroma and its resident vasculature, inflammatory cells, growth factors and the extracellular matrix (ECM), in the development of cancer, and focus on two components as potential therapeutic targets in breast cancer. First, the ECM, which imparts crucial signaling via integrins and other receptors, is a first-line barrier to invasion, modulates aggressive behavior and may be manipulated to provide novel impediments to tumour growth. Second, the authors discuss the involvement of TGF-beta1 as an example of one of many growth factors that can regulate ECM composition and degradation and that play complex roles in cancer. Compared to the variable routes taken by cells to become cancers, the response of tissues to cancer is relatively consistent. Therefore, controlling and eliminating cancer may be more readily achieved indirectly via the tissue microenvironment.

  2. Acting in solidarity: Testing an extended dual pathway model of collective action by bystander group members.

    PubMed

    Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

    2015-09-01

    We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach, 2004). Based on two proposed functions of social identity performance (Klein, Spears, & Reicher, 2007), we distinguished between the efficacy of collective action at consolidating the identity of a protest movement and its efficacy at achieving social change (political efficacy). We expected identity consolidation efficacy to positively predict collective action tendencies directly and indirectly via political efficacy. We also expected collective action tendencies to be positively predicted by moral outrage and by sympathy in response to disadvantaged outgroup's suffering. These hypotheses were supported in two surveys examining intentions to protest for Palestine in Britain (Study 1), and intentions to attend the June 4th vigil in Hong Kong to commemorate the Tiananmen massacre among a sample of Hong Kong citizens (Study 2). The contributions of these findings to research on the dual pathway model of collective action and the different functions of collective action are discussed. PMID:25406712

  3. Teens’ Self-Efficacy to Deal with Dating Violence as Victim, Perpetrator or Bystander

    PubMed Central

    Van Camp, Tinneke; Hébert, Martine; Guidi, Elisa; Lavoie, Francine; Blais, Martin

    2015-01-01

    Multiple studies have demonstrated that adolescent dating violence is highly prevalent and associated with internalizing and externalizing problems. A number of prevention initiatives are being implemented in North-American high schools. Such initiatives do not only aim to raise awareness among potential victims and offenders but also among peer bystanders. Since teenagers mainly reach out to their peers when experiencing adversity, it is important to address adolescents’ efficiency to deal with witnessing dating violence or with friends disclosing dating abuse, in addition to increasing ability to deal with experienced dating violence victimization or perpetration. The aim of this study is to explore adolescents’ self-efficacy to deal with dating violence victimization and perpetration in their relationships and those of their peers. A paper-and-pencil questionnaire was completed by 259 14–18 years olds in Quebec, Canada. The data allows building insight into adolescents’ confidence to reach out for help or to help others in a situation of dating violence victimization and perpetration. We also considered the impact of gender and dating victimization history. Results suggest that dating violence prevention can build on teens’ self-efficacy to deal with dating violence and offer them tools to do so efficiently. PMID:26807554

  4. The HANDDS Program: A Systematic Approach for Addressing Disparities in the Provision of Bystander Cardiopulmonary Resuscitation

    PubMed Central

    Sasson, Comilla; Haukoos, Jason S.; Eigel, Brian; Magid, David J.

    2015-01-01

    The current paradigm of bystander cardiopulmonary resuscitation (CPR) blankets a community with training. Recently, the authors have found that high-risk neighborhoods can be identified, and CPR training can be targeted in the neighborhoods in which it is most needed. This article presents a novel method and pilot implementation trial for the HANDDS (identifying High Arrest Neighborhoods to Decrease Disparities in Survival) program. The authors also seek to describe example methods in which the HANDDS program is being implemented in Denver, Colorado. The HANDDS program uses a simple three-step approach: identify, implement, and evaluate. This systematic conceptual framework uses qualitative and quantitative methods to 1) identify high-risk neighborhoods, 2) understand common barriers to learning and performing CPR in these neighborhoods, and 3) implement and evaluate a train-the-trainer CPR Anytime intervention designed to improve CPR training in these neighborhoods. The HANDDS program is a systematic approach to implementing a community-based CPR training program. Further research is currently being conducted in four large metropolitan U.S. cities to examine whether the results from the HANDDS program can be successfully replicated in other locations. PMID:25269587

  5. Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7.

    PubMed

    Halpert, Matthew M; Konduri, Vanaja; Liang, Dan; Chen, Yunyu; Wing, James B; Paust, Silke; Levitt, Jonathan M; Decker, William K

    2016-05-15

    The remarkable functional plasticity of professional antigen-presenting cells (APCs) allows the adaptive immune system to respond specifically to an incredibly diverse array of potential pathogenic insults; nonetheless, the specific molecular effectors and mechanisms that underpin this plasticity remain poorly characterized. Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), the target of the blockbuster cancer immunotherapeutic ipilimumab, is one of the most well-known and well-studied members of the B7 superfamily and negatively regulates T cell responses by a variety of known mechanisms. Although CTLA-4 is thought to be expressed almost exclusively among lymphoid lineage hematopoietic cells, a few reports have indicated that nonlymphoid APCs can also express the CTLA-4 mRNA transcript and that transcript levels can be regulated by external stimuli. In this study, we substantially build upon these critical observations, definitively demonstrating that mature myeloid lineage dendritic cells (DC) express significant levels of intracellular CTLA-4 that they constitutively secrete in microvesicular structures. CTLA-4(+) microvesicles can competitively bind B7 costimulatory molecules on bystander DC, resulting in downregulation of B7 surface expression with significant functional consequences for downstream CD8(+) T-cell responses. Hence, the data indicate a previously unknown role for DC-derived CTLA-4 in immune cell functional plasticity and have significant implication for the design and implementation of immunomodulatory strategies intended to treat cancer and infectious disease. PMID:26979751

  6. Observational Effects on the Preferences of Children with Autism

    ERIC Educational Resources Information Center

    Leaf, Justin B.; Oppenheim-Leaf, Misty L.; Leaf, Ronald; Courtemanche, Andrea B.; Taubman, Mitchell; McEachin, John; Sheldon, Jan B.; Sherman, James A.

    2012-01-01

    Children with an autism spectrum disorder (ASD) may play with limited objects or toys, making it difficult for teachers to identify reinforcers to use in teaching new skills. The goal of this study was to alter children's preferences from highly preferred toys to toys that were originally less preferred using an observational pairing procedure.…

  7. Response-Specific Effects of Pain Observation on Motor Behavior

    ERIC Educational Resources Information Center

    Morrison, India; Poliakoff, Ellen; Gordon, Lucy; Downing, Paul

    2007-01-01

    How does seeing a painful event happening to someone else influence the observer's own motor system? To address this question, we measured simple reaction times following videos showing noxious or innocuous implements contacting corporeal or noncorporeal objects. Key releases in a go/nogo task were speeded, and key presses slowed, after subjects…

  8. Effect of Information Load and Time on Observational Learning

    ERIC Educational Resources Information Center

    Breslin, Gavin; Hodges, Nicola J.; Williams, A. Mark

    2009-01-01

    We examined whether altering the amount of and moment when visual information is presented affected observational learning for participants practicing a bowling skill. On Day 1, four groups practiced a cricket bowling action. Three groups viewed a full-body point-light model, the model's bowling arm, or between-limb coordination of the model's…

  9. Energetic Particle Precipitation Effects Observed in LIMS Data

    NASA Astrophysics Data System (ADS)

    Holt, L. A.; Randall, C. E.; Harvey, V. L.; Stiller, G. P.; Funke, B.; López-Puertas, M.; Remsberg, E. E.

    2008-12-01

    The Limb Infrared Monitor of the Stratosphere (LIMS) observed stratospheric enhancements in NO2 inside the Arctic polar vortex during the winter of 1978-1979. These enhancements were attributed to the descent of NOx originally produced by precipitating energetic particles in the upper atmosphere. Although few observations of such stratospheric NOx enhancements were made during the decade succeeding the LIMS measurements, investigations in the last decade have shown abundant evidence for these enhancements. Interannual variability in the enhancements appears to be controlled both by the amount of particle precipitation and the prevailing meteorological conditions, which dictate the efficiency with which NOx is transported from the upper atmosphere into the stratosphere. In this presentation, recent satellite measurements of the temporal evolution of NOx in the polar vortex are compared to the LIMS measurements. Our goal is to investigate whether the enhancements were observed by LIMS because of enhanced geomagnetic activity and/or anomalous dynamical conditions, or whether the nighttime observing capability of LIMS simply enabled it to detect the NOx enhancements under nominal conditions.

  10. Fish effects on ocean current observations in the Cariaco Basin

    NASA Astrophysics Data System (ADS)

    Virmani, Jyotika I.; Weisberg, Robert H.

    2009-03-01

    Multiple years of moored current meter observations from the Cariaco Basin show low-frequency variations along with near-inertial waves and further imply the persistent diurnal movement of fish species known to populate the basin. In agreement with short-term observations from 1979, the more recent observations with acoustic Doppler current profilers provide evidence of the multidecadal presence and behavior of these species. An unwanted corollary, however, is a bias in both the vertical and horizontal components of velocity due to the fish movements. Removal of this fish bias results in large data loss (approximately 72%); however, an interpolated, non-biased data set is developed with depth-averaged horizontal velocities comparable to the observations, demonstrating successful elimination of the bias. Further comparisons show that the interpolated data result in minimal variance density loss at low frequencies and a reduction of variance density at high frequencies such that the interpolated data in the internal wave range more closely fit the Garrett-Munk spectrum. The net result is a data set appropriate for further analysis. A mean downward velocity of 0.18 cm s-1 is a reflection of a biogenic particle flux and some residual fish contamination. The mean settling speed of particles in the Cariaco Basin is calculated, via Stokes law, to be smaller than 0.04 cm s-1. Velocity observations from acoustic current meters at depths greater than 400 m are impacted by the water clarity; therefore alternate methods should be used to make velocity measurements at depth.

  11. Doppler effects on velocity spectra observed by MST radars

    NASA Technical Reports Server (NTRS)

    Scheffler, A. O.; Liu, C. H.

    1986-01-01

    Recently, wind data from mesophere-stratosphere-troposphere (MST) radars have been used to study the spectra of gravity waves in the atmosphere (Scheffler and Liu, 1985; VanZandt et al., 1985). Since MST radar measures the line-of-sight Doppler velocities, it senses the components of the wave-associated velocities along its beam directions. These components are related through the polarization relations which depend on the frequency and wave number of the wave. Therfore, the radar-observed velocity spectrum will be different from the original gravity-wave spectrum. Their relationship depends on the frequency and wave number of the wave as well as the propagation geometry. This relation can be used to interpret the observed data. It can also be used to test the assumption of gravity-wave spectrum (Scheffler and Liu, 1985). In deriving this relation, the background atmosphere has been assumed to be motionless. Obviously, the Doppler shift due to the background wind will change the shape of the gravity-wave power spectrum as well as its relation with the radar-observed spectrum. Here, researcher's investigate these changes.

  12. [The Effect of Observation Geometry on Polarized Skylight Spectrum].

    PubMed

    Zhang, Ren-bin; Wang, Ling-mei; Gao, Jun; Wang, Chi

    2015-03-01

    Study on polarized skylight spectral characters while observation geometry changing in different solar zenith angles (SZA), viewing zenith angles (VZA) or relative azimuth angles (RAA). Simulation calculation of cloudless daylight polarimetric spectrum is realized based on the solver, vector discrete ordinate method, of radiative transfer equation. In the Sun's principal and perpendicular plane, the spectral irradiance data, varying at wavelengths in the range between 0.4 and 3 μm, are calculated to extend the atmospheric polarization spectral information under the conditions: the MODTRAN solar reference spectrur is the only illuminant source; the main influencing factors of polarized radiative transfer include underlying surface albedo, aerosol layers and components, and the absorption of trace gases. Simulation analysis results: (1) While the relative azimuth angle is zero, the magnitude of spectrum U/I is lower than 10(-7) and V/I is negligible, the degree of polarization and the spectrum Q/I are shaped like the letter V or mirror-writing U. (2) In twilight, when the Sun is not in FOV of the detector, the polarization of the daytime sky has two maximum near 0.51 and 2.75 μm, and a minimum near 1.5 μm. For arbitrary observation geometry, the spectral signal of V/I may be ignored. According to observation geometry, choosing different spectral bands or polarized signal will be propitious to targets detection. PMID:26117882

  13. Cloud radiative forcing effects on observed and simulated global energetics

    NASA Technical Reports Server (NTRS)

    Sohn, Byung-Ju; Robertson, Franklin

    1993-01-01

    The research objectives are the following: (1) to examine how cloud-radiation processes generate/destroy available potential energy by altering both meridional and zonal temperature gradient; (2) to investigate how the atmospheric dynamic fields respond to the cloud-altered mass distributions through the energy conversion circuit; and (3) to examine how the improved version of CCM1 simulates observationally obtained cloud-radiative forcing and its associated energetics and circulations. Significant accomplishments in the past year towards obtaining these objectives and the focus of current research and plans for next year are discussed.

  14. QUANTIFYING OBSERVATIONAL PROJECTION EFFECTS USING MOLECULAR CLOUD SIMULATIONS

    SciTech Connect

    Beaumont, Christopher N.; Offner, Stella S.R.; Shetty, Rahul; Glover, Simon C. O.; Goodman, Alyssa A.

    2013-11-10

    The physical properties of molecular clouds are often measured using spectral-line observations, which provide the only probes of the clouds' velocity structure. It is hard, though, to assess whether and to what extent intensity features in position-position-velocity (PPV) space correspond to 'real' density structures in position-position-position (PPP) space. In this paper, we create synthetic molecular cloud spectral-line maps of simulated molecular clouds, and present a new technique for measuring the reality of individual PPV structures. Using a dendrogram algorithm, we identify hierarchical structures in both PPP and PPV space. Our procedure projects density structures identified in PPP space into corresponding intensity structures in PPV space and then measures the geometric overlap of the projected structures with structures identified from the synthetic observation. The fractional overlap between a PPP and PPV structure quantifies how well the synthetic observation recovers information about the three-dimensional structure. Applying this machinery to a set of synthetic observations of CO isotopes, we measure how well spectral-line measurements recover mass, size, velocity dispersion, and virial parameter for a simulated star-forming region. By disabling various steps of our analysis, we investigate how much opacity, chemistry, and gravity affect measurements of physical properties extracted from PPV cubes. For the simulations used here, which offer a decent, but not perfect, match to the properties of a star-forming region like Perseus, our results suggest that superposition induces a ∼40% uncertainty in masses, sizes, and velocity dispersions derived from {sup 13}CO (J = 1-0). As would be expected, superposition and confusion is worst in regions where the filling factor of emitting material is large. The virial parameter is most affected by superposition, such that estimates of the virial parameter derived from PPV and PPP information typically disagree

  15. Possible observation of the isotope effect during field evaporation

    NASA Astrophysics Data System (ADS)

    Golubev, O. L.; Blashenkov, N. M.

    2016-01-01

    The field evaporation of tungsten at high temperatures (T ~ 2000 K) has been studied using a magnetic mass spectrometer equipped with a field ion source. Only low-charge ions (W+2 and W+) have been observed in the course of evaporation for all tungsten isotopes. For singly charged ions only, the number of ions of the heaviest isotope, 186W+, was about one order of magnitude lower than that corresponding to the standard isotope ratio for natural tungsten. An explanation of this anomalous phenomenon is proposed.

  16. Experimental observation of melting of the effective Minkowski spacetime

    NASA Astrophysics Data System (ADS)

    Smolyaninov, Igor; Smolyaninova, Vera

    Cobalt nanoparticle-based ferrofluid in the presence of an external magnetic field forms a self-assembled hyperbolic metamaterial, which may be described as an effective 3D Minkowski spacetime for extraordinary photons. Moreover, such extraordinary photons perceive thermal gradients in the ferrofluid as an effective gravitational field, which obeys the Newton law. If the magnetic field is not strong enough, the effective Minkowski spacetime gradually melts under the influence of thermal fluctuations. On the other hand, it may restore itself if the magnetic field is increased back to its original value. Here we present direct microscopic visualization of such a Minkowski spacetime melting/crystallization, which is somewhat similar to hypothesized formation of the Minkowski spacetime in loop quantum cosmology This work was supported in part by NSF Grant DMR-1104676.

  17. Observing the Quantum Spin Hall Effect with Ultracold Atoms

    NASA Astrophysics Data System (ADS)

    Vaishnav, J. Y.; Stanescu, Tudor D.; Clark, Charles W.; Galitski, Victor

    2009-03-01

    The quantum spin Hall (QSH) state is a topologically nontrivial state of matter proposed to exist in certain 2-D systems with spin-orbit coupling. While the electronic states of a QSH insulator are gapped in the bulk, a QSH insulator is characterized by gapless edge states of different spins which counterpropagate at a given edge; the spin is correlated with the direction of propagation. Recent proposals ootnotetextT. D. Stanescu, C. Zhang, V. Galitski, Physical Review Letters 99, 110403 (2007), J. Y. Vaishnav, Charles W. Clark, Physical Review Letters 100, 153002 (2008). suggest that synthetic spin-orbit couplings can be created for cold atoms moving in spatially varying light fields. Here, we identify an optical lattice setup which generates an effective QSH effect for cold, multilevel atoms. We also discuss methods for experimental detection of the atomic QSH effect.

  18. Experimental observation of effects of seeds on polymer crystallization

    NASA Astrophysics Data System (ADS)

    Zhu, Peng-Wei; Phillips, Andy; Edward, Graham; Nichols, Lance

    2009-11-01

    The effects of two seeds on the melt crystallization of isotactic polypropylene were experimentally investigated. The seed, which has the flat surface full of a nonuniform size distribution, has provided a right surface pattern to activate effectively the heterogeneous nucleation. In contrast, the seed, which has the curved surface full of a uniform size distribution, has failed to induce the heterogeneous nucleation. The results from the present work have also shown that the seed with strong nucleating ability leads to the formation of large crystals but the seed without nucleating ability does not influence much the crystal size.

  19. Observational effects of the early episodically dominating dark energy

    NASA Astrophysics Data System (ADS)

    Park, Chan-Gyung; Lee, Jae-heon; Hwang, Jai-chan; Noh, Hyerim

    2014-10-01

    We investigate the observational consequences of the early episodically dominating dark energy on the evolution of cosmological structures. For this aim, we introduce the minimally coupled scalar-field dark energy model with the Albrecht-Skordis potential, which allows a sudden ephemeral domination of a dark energy component during the radiation or early matter era. The conventional cosmological parameters in the presence of such an early dark energy are constrained with WMAP and Planck cosmic microwave background radiation data including other external data sets. It is shown that in the presence of such an early dark energy, the estimated cosmological parameters can deviate substantially from the currently known Λ cold dark matter (Λ CDM )-based parameters, with best-fit values differing by several percent for WMAP and by a percent level for Planck data. For the latter case, only a limited amount of dark energy with episodic nature is allowed since the Planck data strongly favor the Λ CDM model. Compared with the conventional dark energy model, the early dark energy dominating near the radiation-matter equality or at the early matter era results in the shorter cosmic age or the presence of tensor-type perturbation, respectively. Our analysis demonstrates that the alternative cosmological parameter estimation is allowed based on the same observations even in Einstein's gravity.

  20. Possibility of observing dark matter via the gyromagnetic Faraday effect.

    PubMed

    Gardner, Susan

    2008-02-01

    If dark matter consists of cold, neutral particles with a nonzero magnetic moment, then, in the presence of an external magnetic field, a measurable gyromagnetic Faraday effect becomes possible. This enables direct constraints on the nature and distribution of such dark matter through detailed measurements of the polarization and temperature of the cosmic-microwave background radiation. PMID:18352256

  1. Effect of topological defects on "nuclear pasta" observables

    NASA Astrophysics Data System (ADS)

    Schneider, A. S.; Berry, D. K.; Caplan, M. E.; Horowitz, C. J.; Lin, Z.

    2016-06-01

    Background: The "pasta" phase of nuclear matter may play an important role in the structure and evolution of neutron stars. Recent works suggest nuclear pasta has a high resistivity which could be explained by the presence of long-lived topological defects. The defects act as impurities that decrease thermal and electrical conductivity of the pasta. Purpose: To quantify how topological defects affect transport properties of nuclear pasta and estimate this effect using an impurity parameter Qimp. Methods: Contrast molecular dynamics simulations of up to 409 600 nucleons arranged in parallel nuclear pasta slabs (perfect pasta) with simulations of pasta slabs connected by topological defects (impure pasta). From these simulations we compare the viscosity and heat conductivity of perfect and impure pasta to obtain an effective impurity parameter Qimp due to the presence of defects. Results: Both the viscosity and thermal conductivity calculated for both perfect and impure pasta are anisotropic, peaking along directions perpendicular to the slabs and reaching a minimum close to zero parallel to them. In our 409 600 nucleon simulation topological defects connecting slabs of pasta reduce both the thermal conductivity and viscosity on average by about 37%. We estimate an effective impurity parameter due to the defects of order Qimp˜30 . Conclusions: Topological defects in the pasta phase of nuclear matter have an effect similar to impurities in a crystal lattice. The irregularities introduced by the defects reduce the thermal and electrical conductivities and the viscosity of the system. This effect can be parametrized by a large impurity parameter Qimp˜30 .

  2. Directly Observable Behavioral Effects of Lorcaserin in Rats

    PubMed Central

    Serafine, Katherine M.; Rice, Kenner C.

    2015-01-01

    (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032–32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032–1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1–3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. PMID:26384326

  3. Directly Observable Behavioral Effects of Lorcaserin in Rats.

    PubMed

    Serafine, Katherine M; Rice, Kenner C; France, Charles P

    2015-12-01

    (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032-32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032-1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1-3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. PMID:26384326

  4. Observation of relativistic effects in collective Thomson scattering

    SciTech Connect

    Ross, J S; Glenzer, S H; Palastro, J P; Pollock, B B; Price, D; Divol, L; Tynan, G R; Froula, D H

    2009-10-08

    We observe relativistic modifications to the Thomson scattering spectrum in a traditionally classical regime: v{sub osc}/c = eE{sub 0}/cm{omega}{sub 0} << 1 and T{sub e} < 1 keV. The modifications result from scattering off electron-plasma fluctuations with relativistic phase velocities. Normalized phase velocities v/c between 0.03 and 0.12 have been achieved in a N{sub 2} gas-jet plasma by varying the plasma density from 3 x 10{sup 18} cm{sup -3} to 7 x 10{sup 19} cm{sup -3} and electron temperature between 85 eV and 700 eV. For these conditions, the complete temporally resolved Thomson scattering spectrum including the electron and ion features has been measured. A fully relativistic treatment of the Thomson scattering form factor has been developed and shows excellent agreement with the experimental data.

  5. Dust Transport, Deposition and Radiative Effects Observed from MODIS

    NASA Technical Reports Server (NTRS)

    Kaufman, Y. J.; Koren, I.; Remer, L. A.; Tanre, D.; Ginoux, P.; Fan, S.

    2003-01-01

    Carlson (1977) used satellite (AVHRR) observation of dust episodes 3 estimate that 90 tg of dust are emitted from Africa (0-30 N) to the Atlantic Ocean between June and August. MODIS systematic measurements of aerosol optical thickness (AOT) and the fraction of the AOT (f) due to the fine mode (see Remer et al abstract), are used to derive the column concentration, flux and deposition of African dust over the Atlantic Ocean. The main data set is for 2001 but the results are consistent with MODIS measurements from 2002. The analysis first determines the properties of maritime baseline aerosol (AOT=0.06, f=0.5); followed by linear scaling of the dust AOT and the anthropogenic AOT, based on MODIS measured values of the fraction "f" being 0.9 for anthropogenic aerosol and 0.5 for dust. NCEP winds are used in the analysis and are evaluated against observed dust movements between the Terra and Aqua passes (see Koren et al. abstract). Monthly values of dust transport and deposition are calculated. Preliminary results show that 280 tg of dust are emitted annually from Africa to the Atlantic Ocean between 20s and 30N, with 40 tg returning to Africa and Europe between 30N and 50N. 85 tg reach the Americas, with 130-150 tg are deposited in the Atlantic Ocean. The results are compared with dust transport models that indicate 110-230 tg of dust being deposited in the Ocean. It is interesting to note that the early estimates of Carlson (1977) and Carlson & Prosper0 (1972) are very close to our estimate from MODIS of 100 tg for the same latitude range and monthly period.

  6. Observation of the Meissner effect in a lattice Higgs model

    NASA Technical Reports Server (NTRS)

    Damgaard, Poul H.; Heller, Urs M.

    1988-01-01

    The lattice-regularized U(1) Higgs model in an external electromagnetic field is studied by Monte Carlo techniques. In the Coulomb phase, magnetic flux can flow through uniformly. The Higgs phase splits into a region where magnetic flux can penetrate only in the form of vortices and a region where the magnetic flux is completely expelled, the relativistic analog of the Meissner effect in superconductivity. Evidence is presented for symmetry restoration in strong external fields.

  7. Observation of inverse spin Hall effect in ferromagnetic FePt alloys using spin Seebeck effect

    SciTech Connect

    Seki, Takeshi Takanashi, Koki; Uchida, Ken-ichi; Kikkawa, Takashi; Qiu, Zhiyong; Saitoh, Eiji

    2015-08-31

    We experimentally observed the inverse spin Hall effect (ISHE) of ferromagnetic FePt alloys. Spin Seebeck effect due to the temperature gradient generated the spin current (J{sub s}) in the FePt|Y{sub 3}Fe{sub 5}O{sub 12} (YIG) structure, and J{sub s} was injected from YIG to FePt and converted to the charge current through ISHE of FePt. The significant difference in magnetization switching fields for FePt and YIG led to the clear separation of the voltage of ISHE from that of anomalous Nernst effect in FePt. We also investigated the effect of ordering of FePt crystal structure on the magnitude of ISHE voltage in FePt.

  8. Breast feeding and the weekend effect: an observational study

    PubMed Central

    Fitzsimons, Emla; Vera-Hernández, Marcos

    2016-01-01

    Objective To compare the incidence of breast feeding by day of week of birth. Design Retrospective database study using 16 508 records from the 2005 and 2010 Infant Feeding Surveys. Setting England and Wales, UK. Participants Mothers of a sample of births from among all registered births in the periods August–September 2005 and August–October 2010. Main outcome measure Incidence of breast feeding after birth. Results Among babies of mothers who left full-time education aged 16 or under, the incidence of breast feeding was 6.7 percentage points lower (95% CI 1.4 to 12.1 percentage points) for those born on Saturdays than for those born on Mondays–Thursdays. No such differences by day of week of birth were observed among babies of mothers who left school aged 17 or over. Conclusions Breastfeeding policy should take into account differences in breast feeding by day of week of birth, which are apparent among low-educated mothers. Further research is needed to ascertain the reason for this finding. PMID:27401354

  9. Preliminary observation of nonlinear effects in Compton scattering

    SciTech Connect

    Bula, C.; McDonald, K.T.; Prebys, E.J.; E-144 Collaboration

    1996-07-01

    In a new experiment at the Final Focus Test Beam at SLAC a low- emittance 46.6 GeV electron beam is brought into collision with terawatt pulses from a 1.06 {mu} wavelength Nd:glass laser. Peak laser intensities of 10{sup 18} W/cm{sup 2} have been achieved corresponding to a value of 0.6 for the parameter {eta} = {ital eE/mw{sub 0}c}, and to a value of 0.3 for the parameter {Upsilon} = {ital E{sup *}/E{sub crit}} = 2{gamma}{ital ehE}/{ital m}{sup 2}{ital c}{sup 3} in the case of frequency doubled laser pulses. In these circumstances an electron that crosses the center of the laser pulse has near unit interaction probability. Signals are presented for multiphoton Compton scattering in which up to 4 laser photons interact with an electron. High energy backscattered photons of GeV energy can interact within the laser focus to create electron- positron pairs; an excess of 15 positrons above a background of 14 was observed in a run of 6,000 laser shots.

  10. Assessing BMP effectiveness: multiprocedure analysis of observed water quality data.

    PubMed

    Tuppad, Pushpa; Santhi, Chinnasamy; Srinivasan, Raghavan

    2010-11-01

    Observed water quality data obtained from eight stream monitoring locations within Richland-Chambers Watershed in north central Texas were analyzed for trends using box-and-whisker plots, exceedance probability plots, and linear and Mann-Kendall statistical methods. Total suspended solids decreased at seven out of eight stations, and at two of these stations, the decrease was significant. Mixed results were obtained for nitrogen across the stations. A nonsignificant and significant increase in nitrite plus nitrate nitrogen (nitrite+nitrate N) was noticed in two stations each, whereas at the other four stations showed nonsignificant decrease. The results of organic nitrogen (Org N) was similar to nitrite+nitrate N except that the two stations that showed significant increase in nitrite+nitrate N showed nonsignificant decrease in Org N. Mixed results were also noticed for orthophosphorus (Ortho P) including nonsignificant decrease at two stations, significant decrease and increase at one station each, and nonsignificant increase in four stations. In general, total phosphorus (TP) decreased at all stations, significantly at some, except one station where it increased significantly. Decreasing trends in sediment, Org N, Ortho P, and TP were likely related to implementation of best management practices (BMPs). Increasing trends in dissolved constituents including Ortho P and nitrite+nitrate N were likely due to increased surface residue as a result of some BMPs such as conservation tillage. PMID:19936955

  11. Random-effects models for serial observations with binary response

    SciTech Connect

    Stiratelli, R.; Laird, N.; Ware, J.H.

    1984-12-01

    This paper presents a general mixed model for the analysis of serial dichotomous responses provided by a panel of study participants. Each subject's serial responses are assumed to arise from a logistic model, but with regression coefficients that vary between subjects. The logistic regression parameters are assumed to be normally distributed in the population. Inference is based upon maximum likelihood estimation of fixed effects and variance components, and empirical Bayes estimation of random effects. Exact solutions are analytically and computationally infeasible, but an approximation based on the mode of the posterior distribution of the random parameters is proposed, and is implemented by means of the EM algorithm. This approximate method is compared with a simpler two-step method proposed by Korn and Whittemore, using data from a panel study of asthmatics originally described in that paper. One advantage of the estimation strategy described here is the ability to use all of the data, including that from subjects with insufficient data to permit fitting of a separate logistic regression model, as required by the Korn and Whittemore method. However, the new method is computationally intensive.

  12. Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.

    PubMed

    Prado, Noela; Cañamero, Marta; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2010-07-01

    Exosomes represent a new family of bioactive nanovesicles (30-100 nm in diameter) secreted by different cell types whose appealing features can be exploited for designing vaccines in the context of several human diseases. We previously reported the potential of bronchoalveolar lavage fluid (BALF)-derived tolerogenic exosomes (Exo(Tol)) to be used as a nasal allergy vaccine in a mouse model of sensitization to Ole e 1, the main allergen of olive pollen. The aim of the study was to investigate whether such nanovesicles specific to Ole e 1 can also prevent the sensitization to other unrelated allergen, as Bet v 1 from birch pollen. Exo(Tol) were isolated from BALF of mice tolerized against Ole e 1 and used in a prophylactic approach. BALB/c mice were intranasally pretreated with Exo(Tol) one week before sensitization/challenge with Bet v 1, and the magnitude of allergen-specific response was analyzed. Intranasal pretreatment with Exo(Tol) resulted in significant inhibition of both specific IgE and IgG1 antibodies levels. Moreover, T cells from mice pretreated with Exo(Tol) showed a reduction in IL-5 and IL-13 (Th2 cytokines) production. Lung inflammatory response triggered by unrelated allergen-challenge was also significantly reduced after pretreatment: perivascular/peribronchial inflammatory cell infiltration, eosinophilia and mucus secretion. In conclusion, Exo(Tol) specific to Ole e 1, in addition to inhibit specific immune response to this allergen, blocked the allergic response to a second unrelated allergen such as Bet v 1. The in vivo "bystander suppression" that we herein describe for Exo(Tol) may have implications for the treatment of allergy based on mucosal tolerance induction. PMID:20478618

  13. Observation of the underscreened Kondo effect in a molecular transistor.

    PubMed

    Roch, Nicolas; Florens, Serge; Costi, Theo A; Wernsdorfer, Wolfgang; Balestro, Franck

    2009-11-01

    We present the first quantitative experimental evidence for the underscreened Kondo effect, an incomplete compensation of a quantized magnetic moment by conduction electrons, as originally proposed by Nozières and Blandin. The device consists of an even charge spin S=1 molecular quantum dot, obtained by electromigration of C60 molecules into gold nanogaps and operated in a dilution fridge. The persistence of logarithmic singularities in the low temperature conductance is demonstrated by a comparison to the fully screened configuration obtained in odd charge spin S=1/2 Coulomb diamonds. We also discover an extreme sensitivity of the underscreened Kondo resonance to the magnetic field that we confirm on the basis of numerical renormalization group calculations. PMID:20365950

  14. Observation of the Underscreened Kondo Effect in a Molecular Transistor

    NASA Astrophysics Data System (ADS)

    Roch, Nicolas; Florens, Serge; Costi, Theo A.; Wernsdorfer, Wolfgang; Balestro, Franck

    2009-11-01

    We present the first quantitative experimental evidence for the underscreened Kondo effect, an incomplete compensation of a quantized magnetic moment by conduction electrons, as originally proposed by Nozières and Blandin. The device consists of an even charge spin S=1 molecular quantum dot, obtained by electromigration of C60 molecules into gold nanogaps and operated in a dilution fridge. The persistence of logarithmic singularities in the low temperature conductance is demonstrated by a comparison to the fully screened configuration obtained in odd charge spin S=1/2 Coulomb diamonds. We also discover an extreme sensitivity of the underscreened Kondo resonance to the magnetic field that we confirm on the basis of numerical renormalization group calculations.

  15. Observational Effects of Magnetism in O Stars: Surface Nitrogen Abundances

    NASA Technical Reports Server (NTRS)

    Martins, F.; Escolano, C.; Wade, G. A.; Donati, J. F.; Bouret, J. C.

    2011-01-01

    Aims. We investigate the surface nitrogen content of the six magnetic O stars known to date as well as of the early B-type star Tau Sco.. We compare these abundances to predictions of evolutionary models to isolate the effects of magnetic field on the transport of elements in stellar interiors. Methods. We conduct a quantitative spectroscopic analysis of the ample stars with state-of-the-art atmosphere models. We rely on high signal-to-noise ratio, high resolution optical spectra obtained with ESPADONS at CFHT and NARVAL at TBL. Atmosphere models and synthetic spectra are computed with the code CMFGEN. Values of N/H together with their uncertainties are determined and compared to predictions of evolutionary models. Results. We find that the magnetic stars can be divided into two groups: one with stars displaying no N enrichment (one object); and one with stars most likely showing extra N enrichment (5 objects). For one star (Ori C) no robust conclusion can be drawn due to its young age. The star with no N enrichment is the one with the weakest magnetic field, possibly of dynamo origin. It might be a star having experienced strong magnetic braking under the condition of solid body rotation, but its rotational velocity is still relatively large. The five stars with high N content were probably slow rotators on the zero age main sequence, but they have surface N/H typical of normal O stars, indicating that the presence of a (probably fossil) magnetic field leads to extra enrichment. These stars may have a strong differential rotation inducing shear mixing. Our results shOuld be viewed as a basis on which new theoretical simulations can rely to better understand the effect of magnetism on the evolution of massive stars.

  16. The Effect of Different Modes of Task Orientation on Observational Attainment in Practical Chemistry

    ERIC Educational Resources Information Center

    Kempa, R. F.; Ward, J. E.

    1975-01-01

    Examines the effect of three different modes of task orientation on observational attainment in practical chemistry. Results include the overall performance on the chemistry observation test and an analysis of the influence of the complexity of observational tasks on observational attainment. (Author/GS)

  17. Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes.

    PubMed

    Pane, Jessica A; Coulson, Barbara S

    2015-06-01

    Viruses are considered to be potential key modulators of type 1 diabetes mellitus, with several possible mechanisms proposed for their modes of action. Here we discuss the evidence for virus involvement, including pancreatic infection and the induction of T cell-mediated molecular mimicry. A particular focus of this review is the further possibility that virus infection triggers bystander activation of pre-existing autoreactive lymphocytes. In this scenario, the virus triggers dendritic cell maturation and proinflammatory cytokine secretion by engaging pattern recognition receptors. These proinflammatory cytokines provoke bystander autoreactive lymphocyte activation in the presence of cognate autoantigen, which leads to enhanced beta cell destruction. Importantly, this mechanism does not necessarily involve pancreatic virus infection, and its virally non-specific nature suggests that it might represent a means commonly employed by multiple viruses. The ability of viruses specifically associated with type 1 diabetes, including group B coxsackievirus, rotavirus and influenza A virus, to induce these responses is also examined. The elucidation of a mechanism shared amongst several viruses for accelerating progression to type 1 diabetes would facilitate the identification of important targets for disease intervention. PMID:25794781

  18. The Effects of Observational Learning on Preschoolers' Book-Related Behaviors and Alphabet Knowledge.

    ERIC Educational Resources Information Center

    Horner, Sherri L.

    2001-01-01

    Investigated effects of observational learning on preschoolers' attention to print, use of a questioning technique, and knowledge of the alphabet. Found that young children are able to extract a concept or rule through a brief exposure to observational learning. (SD)

  19. Noble or Malevolent in a Moment of Dismay: How Postsecondary Students Construe and Characterize Bystander Action in School Violence Shooting Incidents

    ERIC Educational Resources Information Center

    Underhill, Dyan Whitlow

    2012-01-01

    Multiple incidents of postsecondary school shooting violence have occurred in American society--prompting concern about safety on college campuses, administrators' roles in prevention, and proactive and responsible bystander actions. Active shooter plans have become more established in educational environments, with efforts are directed…

  20. Influence of Psychological and Social Factors on Bystanders' Roles in School Bullying among Korean-American Students in the United States

    ERIC Educational Resources Information Center

    Choi, Sumi; Cho, Young Il

    2013-01-01

    This study investigated the associations of psychological and social variables with the likelihood of exhibiting three different behaviors as a bystander in a bullying situation. The sample comprised 238 Korean-American and Korean students, from the 3rd to 12th grades, studying in the USA. Students receiving classmate support showed a lower…

  1. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors.

    PubMed

    Leten, Cindy; Trekker, Jesse; Struys, Tom; Roobrouck, Valerie D; Dresselaers, Tom; Vande Velde, Greetje; Lambrichts, Ivo; Verfaillie, Catherine M; Himmelreich, Uwe

    2016-01-01

    Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents. PMID:26880961

  2. BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard the use of biologically based dose-response models is particularly advocated. The aim is to pr...

  3. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

    PubMed Central

    Leten, Cindy; Trekker, Jesse; Struys, Tom; Roobrouck, Valerie D.; Dresselaers, Tom; Vande Velde, Greetje; Lambrichts, Ivo; Verfaillie, Catherine M.; Himmelreich, Uwe

    2016-01-01

    Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents. PMID:26880961

  4. Investigating the influence of respiratory motion on the radiation induced bystander effect in modulated radiotherapy

    NASA Astrophysics Data System (ADS)

    Cole, Aidan J.; McGarry, Conor K.; Butterworth, Karl T.; McMahon, Stephen J.; Hounsell, Alan R.; Prise, Kevin M.; O'Sullivan, Joe M.

    2013-12-01

    Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy and may contribute towards uncertainties in radiotherapy planning. This study investigates the potential radiobiological implications occurring due to tumour motion in areas of geometric miss in lung cancer radiotherapy. A bespoke phantom and motor-driven platform to replicate respiratory motion and study the consequences on tumour cell survival in vitro was constructed. Human non-small-cell lung cancer cell lines H460 and H1299 were irradiated in modulated radiotherapy configurations in the presence and absence of respiratory motion. Clonogenic survival was calculated for irradiated and shielded regions. Direction of motion, replication of dosimetry by multi-leaf collimator (MLC) manipulation and oscillating lead shielding were investigated to confirm differences in cell survival. Respiratory motion was shown to significantly increase survival for out-of-field regions for H460/H1299 cell lines when compared with static irradiation (p < 0.001). Significantly higher survival was found in the in-field region for the H460 cell line (p < 0.030). Oscillating lead shielding also produced these significant differences. Respiratory motion and oscillatory delivery of radiation dose to human tumour cells has a significant impact on in- and out-of-field survival in the presence of non-uniform irradiation in this in vitro set-up. This may have important radiobiological consequences for modulated radiotherapy in lung cancer.

  5. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    SciTech Connect

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  6. Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection▿

    PubMed Central

    Meythaler, Mareike; Martinot, Amanda; Wang, Zichun; Pryputniewicz, Sarah; Kasheta, Melissa; Ling, Binhua; Marx, Preston A.; O'Neil, Shawn; Kaur, Amitinder

    2009-01-01

    In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8+ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8+ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4+ and CD4−CD8− T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection. PMID:18987149

  7. Observations of dust acoustic waves driven at high frequencies: Finite dust temperature effects and wave interference

    SciTech Connect

    Thomas, Edward Jr.; Fisher, Ross; Merlino, Robert L.

    2007-12-15

    An experiment has been performed to study the behavior of dust acoustic waves driven at high frequencies (f>100 Hz), extending the range of previous work. In this study, two previously unreported phenomena are observed--interference effects between naturally excited dust acoustic waves and driven dust acoustic waves, and the observation of finite dust temperature effects on the dispersion relation.

  8. The Effects of Three Methods of Observation on Couples in Interactional Research.

    ERIC Educational Resources Information Center

    Carpenter, Linda J.; Merkel, William T.

    1988-01-01

    Assessed the effects of three different methods of observation of couples (one-way mirror, audio recording, and video recording) on 30 volunteer, nonclinical married couples. Results suggest that types of observation do not produce significantly different effects on nonclinical couples. (Author/ABL)

  9. Mixed-Effects Logistic Regression for Estimating Transitional Probabilities in Sequentially Coded Observational Data

    ERIC Educational Resources Information Center

    Ozechowski, Timothy J.; Turner, Charles W.; Hops, Hyman

    2007-01-01

    This article demonstrates the use of mixed-effects logistic regression (MLR) for conducting sequential analyses of binary observational data. MLR is a special case of the mixed-effects logit modeling framework, which may be applied to multicategorical observational data. The MLR approach is motivated in part by G. A. Dagne, G. W. Howe, C. H.…

  10. Removal of seeing and instrumental blur effects from astronomical scanner observations

    NASA Technical Reports Server (NTRS)

    Clements, A. E.; Herman, B. M.

    1974-01-01

    The Phillips-Twomey method for solving simultaneous integral equations is applied to the problem of removing blur effects arising from atmospheric and instrumental sources from astronomical observations made with photoelectric area-scanning instruments. Details of the method and the effects of observational errors on the quality of the results are discussed in the context of applications to actual observations of stars and the planet Saturn.

  11. Observed geomagnetic induction effect on Dst-related magnetic observations under different disturbance intensities of the magnetospheric ring current

    NASA Astrophysics Data System (ADS)

    Xu, Dan; Chen, Huaran; Gao, Mengtan

    2015-01-01

    Based on the spherical harmonic expansion of geomagnetic disturbance observed on the mid-latitude surface of the Earth, external and internal field separation is conducted in which the external component is magnetic disturbance caused by the magnetospheric ring current and the internal component is that raised by the correspondingly induced currents within the Earth. The objectives are to evaluate the influences of the induced internal field on the surface magnetic observations and to reveal the response performance of internal geomagnetic induction under different strengths of magnetospheric ring current fluctuations for better understanding of the disturbance storm time ( Dst) index variations. The results show that the ratio of the internal component to surface observation does not remain constant in storm time. During the main phase of the storm, the ratio variation follows the pattern of logarithmic growth with storm evolution up to the top value at the Dst-minimum; then, the ratio slowly decreases in the long recovery phase. Multiple small logarithmic growths are superimposed on the traces of internal ratios, corresponding to temporary ring current intensification during the storm main phase and amplifying the effect of this intensification on surface magnetic observations. With the intensification of magnetospheric storms from the level of (-200 nT, - 100 nT) to (-300 nT, - 200 nT) and (-500 nT, - 300 nT) classified with the Dst-minimum, the top value of the ratio averaged for each storm group in the superposed epoch analysis method increases from the value of 0.295 ± 0.014 to 0.300 ± 0.016 and 0.308 ± 0.015, respectively. It is demonstrated that the geomagnetic induction exceeds the linear relation with the intensification of the external field, which is physically reasonable and coincident with the Faraday's law of induction. Due to the effects of high induction of the oceans and lateral heterogeneity of electric conductivity distribution in the upper

  12. Effect of tropical cyclones on the stratosphere-troposphere exchange observed using satellite observations over the north Indian Ocean

    NASA Astrophysics Data System (ADS)

    Venkat Ratnam, M.; Babu, S. Ravindra; Das, S. S.; Basha, G.; Krishnamurthy, B. V.; Venkateswararao, B.

    2016-07-01

    Tropical cyclones play an important role in modifying the tropopause structure and dynamics as well as stratosphere-troposphere exchange (STE) processes in the upper troposphere and lower stratosphere (UTLS) region. In the present study, the impact of cyclones that occurred over the north Indian Ocean during 2007-2013 on the STE processes is quantified using satellite observations. Tropopause characteristics during cyclones are obtained from the Global Positioning System (GPS) radio occultation (RO) measurements, and ozone and water vapour concentrations in the UTLS region are obtained from Aura Microwave Limb Sounder (MLS) satellite observations. The effect of cyclones on the tropopause parameters is observed to be more prominent within 500 km of the centre of the tropical cyclone. In our earlier study, we observed a decrease (increase) in the tropopause altitude (temperature) up to 0.6 km (3 K), and the convective outflow level increased up to 2 km. This change leads to a total increase in the tropical tropopause layer (TTL) thickness of 3 km within 500 km of the centre of cyclone. Interestingly, an enhancement in the ozone mixing ratio in the upper troposphere is clearly noticed within 500 km from the cyclone centre, whereas the enhancement in the water vapour in the lower stratosphere is more significant on the south-east side, extending from 500 to 1000 km away from the cyclone centre. The cross-tropopause mass flux for different intensities of cyclones is estimated and it is found that the mean flux from the stratosphere to the troposphere for cyclonic storms is 0.05 ± 0.29 × 10-3 kg m-2, and for very severe cyclonic storms it is 0.5 ± 1.07 × 10-3 kg m-2. More downward flux is noticed on the north-west and south-west side of the cyclone centre. These results indicate that the cyclones have significant impact in effecting the tropopause structure, ozone and water vapour budget, and consequentially the STE in the UTLS region.

  13. Converting Soil Moisture Observations to Effective Values for Improved Validation of Remotely Sensed Soil Moisture

    NASA Technical Reports Server (NTRS)

    Laymon, Charles A.; Crosson, William L.; Limaye, Ashutosh; Manu, Andrew; Archer, Frank

    2005-01-01

    We compare soil moisture retrieved with an inverse algorithm with observations of mean moisture in the 0-6 cm soil layer. A significant discrepancy is noted between the retrieved and observed moisture. Using emitting depth functions as weighting functions to convert the observed mean moisture to observed effective moisture removes nearly one-half of the discrepancy noted. This result has important implications in remote sensing validation studies.

  14. Comparison of ventilation and chest compression performance by bystanders using the Impact Model 730 ventilator and a conventional bag valve with mask in a model of adult cardiopulmonary arrest.

    PubMed

    Hurst, Victor; West, Sarah; Austin, Paul; Branson, Richard; Beck, George

    2007-04-01

    "Bystanders" or lay persons are typically the first caregivers to attend to a victim of out-of-hospital cardiopulmonary arrest. Astronaut crew medical officers (CMO) play a similar role to bystanders aboard the International Space Station (ISS). Studies have demonstrated the importance of bystander cardiopulmonary resuscitation (BCPR) for patient survival before the arrival of emergency medical care. Recent apprehension from bystanders about the threat of contracting communicable diseases during BCPR, however, has led to the consideration of other ventilation systems such as the bag-valve mask (BVM) and automatic transport ventilators (ATV). BVM use is called for during CPR aboard the ISS. This study evaluated the ventilation and compression performance of 40 basic CPR-trained bystanders using either a BVM (adult-sized self-inflating bag with face mask) or an ATV (Model 730 ventilator (M730), Impact Instrumentation, Inc., West Caldwell, NJ). Each two-bystander team gave BCPR to a simulated cardiopulmonary arrest victim using the 2-breath/15-compression cycle for 4 min and then switched roles for another 4-min interval. Compared to BVM use, the M730 led to significantly (p<0.05) lower number of breaths, smaller tidal volumes, airway flows, airway pressures, volume of gas entering the stomach per breath and chest compressions for the 4-min period. The M730 also enabled a bystander to meet the recommendation of 4-breath and compression cycles per minute as per Guidelines 2000. Lastly, ease-of-use scores were significantly higher for the M730 compared to the BVM. Overall, the data suggest that the M730 improves the quality of performance for a bystander performing BCPR. PMID:17175090

  15. NLRP3 inflammasome activation drives bystander cone photoreceptor cell death in a P23H rhodopsin model of retinal degeneration.

    PubMed

    Viringipurampeer, Ishaq A; Metcalfe, Andrew L; Bashar, Abu E; Sivak, Olena; Yanai, Anat; Mohammadi, Zeinabsadat; Moritz, Orson L; Gregory-Evans, Cheryl Y; Gregory-Evans, Kevin

    2016-04-15

    The molecular signaling leading to cell death in hereditary neurological diseases such as retinal degeneration is incompletely understood. Previous neuroprotective studies have focused on apoptotic pathways; however, incomplete suppression of cell death with apoptosis inhibitors suggests that other mechanisms are at play. Here, we report that different signaling pathways are activated in rod and cone photoreceptors in the P23H rhodopsin mutant rat, a model representing one of the commonest forms of retinal degeneration. Up-regulation of the RIP1/RIP3/DRP1 axis and markedly improved survival with necrostatin-1 treatment highlighted necroptosis as a major cell-death pathway in degenerating rod photoreceptors. Conversely, up-regulation of NLRP3 and caspase-1, expression of mature IL-1β and IL-18 and improved cell survival with N-acetylcysteine treatment suggested that inflammasome activation and pyroptosis was the major cause of cone cell death. This was confirmed by generation of the P23H mutation on an Nlrp3-deficient background, which preserved cone viability. Furthermore, Brilliant Blue G treatment inhibited inflammasome activation, indicating that the 'bystander cell death' phenomenon was mediated through the P2RX7 cell-surface receptor. Here, we identify a new pathway in cones for bystander cell death, a phenomenon important in development and disease in many biological systems. In other retinal degeneration models different cell-death pathways are activated, which suggests that the particular pathways that are triggered are to some extent genotype-specific. This also implies that neuroprotective strategies to limit retinal degeneration need to be customized; thus, different combinations of inhibitors will be needed to target the specific pathways in any given disease. PMID:27008885

  16. Observability of the bulk Casimir effect: Can the dynamical Casimir effect be relevant to sonoluminescence?

    SciTech Connect

    Milton, K.A.; Jack Ng, Y.

    1998-05-01

    The experimental observation of intense light emission by acoustically driven, periodically collapsing bubbles of air in water (sonoluminescence) has yet to receive an adequate explanation. One of the most intriguing ideas is that the conversion of acoustic energy into photons occurs quantum mechanically, through a dynamical version of the Casimir effect. We have argued elsewhere that in the adiabatic approximation, which should be reliable here, Casimir or zero-point energies cannot possibly be large enough to be relevant. (About 10 MeV of energy is released per collapse.) However, there are sufficient subtleties involved that others have come to opposite conclusions. In particular, it has been suggested that bulk energy, that is, simply the naive sum of (1) /(2) {h_bar}{omega}, which is proportional to the volume, could be relevant. We show that this cannot be the case, based on general principles as well as specific calculations. In the process we further illuminate some of the divergence difficulties that plague Casimir calculations, with an example relevant to the bag model of hadrons. {copyright} {ital 1998} {ital The American Physical Society}

  17. Mixed-Effects Logistic Regression Models for Indirectly Observed Discrete Outcome Variables

    ERIC Educational Resources Information Center

    Vermunt, Jeroen K.

    2005-01-01

    A well-established approach to modeling clustered data introduces random effects in the model of interest. Mixed-effects logistic regression models can be used to predict discrete outcome variables when observations are correlated. An extension of the mixed-effects logistic regression model is presented in which the dependent variable is a latent…

  18. The effect of negative stimulus presentations on observing-response rates

    PubMed Central

    Mueller, Kay L.; Dinsmoor, James A.

    1986-01-01

    Theories of observing differ in predicting whether or not a signal for absence of reinforcement (S−) is capable of reinforcing observing responses. Experiments in which S− was first removed from and then restored to the procedure have yielded mixed results. The present experiments suggest that failure to control for the direct effect of presenting S− may have been responsible. Pigeons and operant procedures were used. Experiment 1 showed that presentations of S−, even when not contingent on observing, can raise the rate of an observing response that was reinforced only by presentations of a signal (S+) that accompanied a schedule of food delivery. Experiment 2 showed that this effect resulted from bursts of responding that followed offsets of S−. Experiment 3 showed that, when the presence of S− was held constant, lower rates occurred when S− was dependent on, rather than independent of, observing. These results support theories that characterize S− as incapable of reinforcing observing responses. PMID:16812463

  19. The rotation of the Sun: Observations at Stanford. [using the Doppler effect

    NASA Technical Reports Server (NTRS)

    Scherrer, J. M.; Wilcox, J. M.; Svalgaard, L.

    1980-01-01

    Daily observations of the photospheric rotation rate using the Doppler effect made at the Stanford Solar Observatory since May 1976 are analyzed. Results show that these observations show no daily or long period variations in the rotation rate that exceed the observational error of about one percent. The average rotation rate is the same as that of the sunspot and the large-scale magnetic field structures.

  20. Parallax and atmospheric scattering effects on the inversion of satellite auroral observations

    NASA Astrophysics Data System (ADS)

    Abreu, V. J.; Hays, P. B.

    1981-07-01

    A technique for the inversion of satellite auroral brightness observations is developed, which takes into account the backscattering of light from the snow-covered ground and atmospheric scattering. The theory includes parallax effects. Parallax arises when a point in the aurora is observed from different angles against a background with a variable brightness. It is shown that observations from a spinning satellite at any given angle from nadir are sufficient to recover the auroral form.

  1. Parallax and atmospheric scattering effects on the inversion of satellite auroral observations

    NASA Technical Reports Server (NTRS)

    Abreu, V. J.; Hays, P. B.

    1981-01-01

    A technique for the inversion of satellite auroral brightness observations is developed, which takes into account the backscattering of light from the snow-covered ground and atmospheric scattering. The theory includes parallax effects. Parallax arises when a point in the aurora is observed from different angles against a background with a variable brightness. It is shown that observations from a spinning satellite at any given angle from nadir are sufficient to recover the auroral form.

  2. The earth's radiation budget and its relation to atmospheric hydrology. I - Observations of the clear sky greenhouse effect. II - Observations of cloud effects

    NASA Technical Reports Server (NTRS)

    Stephens, Graeme L.; Greenwald, Thomas J.

    1991-01-01

    The clear-sky components of the earth's radiation budget (ERB), the relationship of these components to the sea surface temperature (SST), and microwave-derived water-vapor amount are analyzed in an observational study along with the relationship between the cloudy-sky components of ERB and space/time coincident observations of SST, microwave-derived cloud liquid water, and cloud cover. The purpose of the study is to use these observations for establishing an understanding of the couplings between radiation and the atmosphere that are important to understanding climate feedback. A strategy for studying the greenhouse effect of earth by analyzing the emitted clear-sky longwave flux over the ocean is proposed. It is concluded that the largest observed influence of clouds on ERB is more consistent with macrophysical properties of clouds as opposed to microphysical properties. The analysis for clouds and the greenhouse effect of clouds is compared quantitatively with the clear sky results. Land-ocean differences and tropical-midlatitude differences are shown and explained in terms of the cloud macrostructure.

  3. Guided Field Observations: Variables Related to Preservice Teachers' Knowledge about Effective Primary Reading Instruction

    ERIC Educational Resources Information Center

    Roehrig, Alysia D.; Guidry, Lisa O.; Bodur, Yasar; Guan, Qun; Guo, Ying; Pop, Margareta

    2008-01-01

    Relations between preservice teachers' guided field observations of primary literacy instruction and knowledge about effective beginning reading practices were explored. Preservice teachers (n = 48) participated in a Directed Field Experience course including instruction on and observations of exemplary teaching practices promoting student…

  4. Empirically Driven Variable Selection for the Estimation of Causal Effects with Observational Data

    ERIC Educational Resources Information Center

    Keller, Bryan; Chen, Jianshen

    2016-01-01

    Observational studies are common in educational research, where subjects self-select or are otherwise non-randomly assigned to different interventions (e.g., educational programs, grade retention, special education). Unbiased estimation of a causal effect with observational data depends crucially on the assumption of ignorability, which specifies…

  5. Observational Learning and Its Effects on the Orchestration of Writing Processes

    ERIC Educational Resources Information Center

    Braaksma, Martine A. H.; Rijlaarsdam, Gert; van den Bergh, Huub; van Hout-Wolters, Bernadette H. A. M

    2004-01-01

    In this study, we examined why observational learning positively affects learning outcomes of new writing tasks. In this study, we focused on the effects of observational learning on the temporal organization (i.e., orchestration) of writing processes and on the subsequent influence on text quality. An experiment was set up in which participants…

  6. The Effect of Observational Learning on Students' Performance, Processes, and Motivation in Two Creative Domains

    ERIC Educational Resources Information Center

    Groenendijk, Talita; Janssen, Tanja; Rijlaarsdam, Gert; van den Bergh, Huub

    2013-01-01

    Background. Previous research has shown that observation can be effective for learning in various domains, for example, argumentative writing and mathematics. The question in this paper is whether observational learning can also be beneficial when learning to perform creative tasks in visual and verbal arts. Aims. We hypothesized that observation…

  7. Effects of Playing versus Observing Violent versus Nonviolent Video Games on Children's Aggression.

    ERIC Educational Resources Information Center

    Graybill, Daniel; And Others

    1987-01-01

    Examined short-term effects of playing versus observing violent versus nonviolent video games on the aggression of elementary school children. Children (N=146) played or observed games for 14 minutes, then completed three measures of aggression. Found no differences between violent and nonviolent conditions on measures of aggression. (Author/NB)

  8. Effect of wind gusts on the motion of a balloon-borne observation platform

    NASA Technical Reports Server (NTRS)

    Nigro, N. J.; Johanek, F. M.

    1982-01-01

    The effect of wind gusts on the magnitude of the pendulation angles of a balloon-borne observation platform is determined. A system mathematical model is developed and the solution of this model is used to determine the magnitude of the observation platforms pendulation angles.

  9. Effects of Observing Eye Contact on Gaze Following in High-Functioning Autism

    ERIC Educational Resources Information Center

    Böckler, Anne; Timmermans, Bert; Sebanz, Natalie; Vogeley, Kai; Schilbach, Leonhard

    2014-01-01

    Observing eye contact between others enhances the tendency to subsequently follow their gaze and has been suggested to function as a social signal that adds meaning to an upcoming action or event. The present study investigated effects of observed eye contact in high-functioning autism (HFA). Two faces on a screen either looked at or away from…

  10. Understanding the Greenhouse Effect Using Clear vs Cloudy Sky Diurnal Temperature Observations

    NASA Astrophysics Data System (ADS)

    Tayor, S. V.

    2006-12-01

    Standard meteorological observations from local airports can provide a tangible example of how the greenhouse effect is a part of everyday life. In the exercise outlined here, students plot diurnal temperature observations to compare the relative magnitude of the greenhouse effect under clear and cloudy-sky conditions, gaining insight into the strength of the greenhouse effect. Contemplation of the relation of surface temperature and humidity with cloud cover leads to a further understading of important atmospheric processes involving the Clausius-Clapeyron equation and terrestrial and solar radiation effects.

  11. Observation of Rayleigh-Taylor-instability evolution in a plasma with magnetic and viscous effects

    DOE PAGESBeta

    Adams, Colin S.; Moser, Auna L.; Hsu, Scott C.

    2015-11-06

    We present time-resolved observations of Rayleigh-Taylor-instability (RTI) evolution at the interface between an unmagnetized plasma jet colliding with a stagnated, magnetized plasma. The observed instability growth time (~10μs) is consistent with the estimated linear RTI growth rate calculated using experimentally inferred values of density (~1014cm–3) and deceleration (~109 m/s2). The observed mode wavelength (≳1 cm) nearly doubles within a linear growth time. Furthermore, theoretical estimates of magnetic and viscous stabilization and idealized magnetohydrodynamic simulations including a physical viscosity model both suggest that the observed instability evolution is subject to magnetic and/or viscous effects.

  12. Observation of Rayleigh-Taylor-instability evolution in a plasma with magnetic and viscous effects

    NASA Astrophysics Data System (ADS)

    Adams, Colin S.; Moser, Auna L.; Hsu, Scott C.

    2015-11-01

    We present time-resolved observations of Rayleigh-Taylor-instability (RTI) evolution at the interface between an unmagnetized plasma jet colliding with a stagnated, magnetized plasma. The observed instability growth time (˜10 μ s ) is consistent with the estimated linear RTI growth rate calculated using experimentally inferred values of density (˜1014cm-3 ) and deceleration (˜109 m /s2). The observed mode wavelength (≳1 cm) nearly doubles within a linear growth time. Theoretical estimates of magnetic and viscous stabilization and idealized magnetohydrodynamic simulations including a physical viscosity model both suggest that the observed instability evolution is subject to magnetic and/or viscous effects.

  13. Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery.

    PubMed

    Tanaka, Megumi; Kubota, Shinji; Onmyoji, Yusuke; Hirano, Masato; Uehara, Kazumasa; Morishita, Takuya; Funase, Kozo

    2015-07-23

    We aimed to investigate the effects of the tactile stimulation to an observer's fingertips at the moment that they saw an object being pinched by another person on the excitability of observer's primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects' right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects' first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer's fingertips at the moment corresponding to the pinching being observed. PMID:26033185

  14. Finite field of view effects on inversion of limb thermal emission observations. [balloon sounding of stratosphere

    NASA Technical Reports Server (NTRS)

    Abbas, M. M.; Guo, J.; Conrath, B. J.; Kunde, V. G.; Maguire, W. C.

    1985-01-01

    It is pointed out that the technique of thermal emission spectroscopy provides an effective means for remote sounding of stratospheric temperature structure and constituent distributions. One procedure for measuring the stratospheric infrared spectrum involves the conduction of observations along ray paths tangent to the stratospheric limb. Thermal emission limb tangent observations have certain advantages compared to other types of observations. The techniques for determining temperature and trace gas distributions from limb thermal emission radiances are based on the assumption that the bulk of opacity lies near the tangent point. Ideally, the field of view (FOV) of the observing instrument should be very small. The effect of a finite FOV is to reduce the spatial resolution of the retrieved temperature and constituent profiles. The present investigation is concerned with the effects of the FOV on the inversion of infrared thermal emission measurements for balloon platforms. Attention is given to a convenient method for determining the weighting functions.

  15. The Effects of Training, Feedback, and Participant Involvement in Behavioral Safety Observations on Office Ergonomic Behavior

    ERIC Educational Resources Information Center

    Sasson, Joseph R.; Austin, John

    2005-01-01

    Eleven computer terminal operators participated in an experiment that assessed effects of several interventions aimed at increasing safe ergonomic performance. All participants received ergonomics training and performance feedback while six of them collected observations of safe behavior among the remaining five participants. Effects of…

  16. Explanation of the Inverse Doppler Effect Observed in Nonlinear Transmission Lines

    SciTech Connect

    Kozyrev, Alexander B.; Weide, Daniel W. van der

    2005-05-27

    The theory of the inverse Doppler effect recently observed in magnetic nonlinear transmission lines is developed. We explain the crucial role of the backward spatial harmonic in the occurrence of an inverse Doppler effect and draw analogies of the magnetic nonlinear transmission line to the backward wave oscillator.

  17. The Effects of Observational Training on the Acquisition of Reinforcement for Listening

    ERIC Educational Resources Information Center

    Lawson, Tracy Reilly; Walsh, Darcy

    2007-01-01

    Experiment 1 investigated the effects of observational training in a social listener reinforcement game on participants' conversational units in non-instructional settings. Experiment 2 tested the effects of multiple exemplar instruction on the development of "empathy." The participants who had reader/writer levels of verbal behavior were selected…

  18. Effect of Grouping of Evidence Types on Learning about Interactions between Observed and Unobserved Causes

    ERIC Educational Resources Information Center

    Rottman, Benjamin Margolin; Ahn, Woo-kyoung

    2011-01-01

    When a cause interacts with unobserved factors to produce an effect, the contingency between the observed cause and effect cannot be taken at face value to infer causality. Yet it would be computationally intractable to consider all possible unobserved, interacting factors. Nonetheless, 6 experiments found that people can learn about an unobserved…

  19. Effects of LatticeQCD EoS and Continuous Emission on Some Observables

    SciTech Connect

    Hama, Y.; Andrade, R.; Grassi, F.; Socolowski, O.; Kodama, T.; Tavares, B.; Padula, S. S.

    2006-04-11

    Effects of lattice-QCD-inspired equations of state and continuous emission on some observables are discussed, by solving a 3D hydrodynamics. The particle multiplicity as well {nu} 2 are found to increase in the mid-rapidity. We also discuss the effects of the initial-condition fluctuations.

  20. Litomosoides sigmodontis induces TGF-β receptor responsive, IL-10-producing T cells that suppress bystander T-cell proliferation in mice.

    PubMed

    Hartmann, Wiebke; Schramm, Christoph; Breloer, Minka

    2015-09-01

    Helminth parasites suppress immune responses to prolong their survival within the mammalian host. Thereby not only helminth-specific but also nonhelminth-specific bystander immune responses are suppressed. Here, we use the murine model of Litomosoides sigmodontis infection to elucidate the underlying mechanisms leading to this bystander T-cell suppression. When OT-II T cells specific for the third-party antigen ovalbumin are transferred into helminth-infected mice, these cells respond to antigen-specific stimulation with reduced proliferation compared to activation within non-infected mice. Thus, the presence of parasitic worms in the thoracic cavity translates to suppression of T cells with a different specificity at a different site. By eliminating regulatory receptors, cytokines, and cell populations from this system, we provide evidence for a two-staged process. Parasite products first engage the TGF-β receptor on host-derived T cells that are central to suppression. In a second step, host-derived T cells produce IL-10 and subsequently suppress the adoptively transferred OT-II T cells. Terminal suppression was IL-10-dependant but independent of intrinsic TGF-β receptor- or PD-1-mediated signaling in the suppressed OT-II T cells. Blockade of the same key suppression mediators, i.e. TGF-β- and IL-10 receptor, also ameliorated the suppression of IgG response to bystander antigen vaccination in L. sigmodontis-infected mice. PMID:26138667