Bystander Effect Research Papers - Academia.edu (original) (raw)

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... more

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 bystan...

The aim of the current study was to examine whether moral disengagement and defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with defending and reinforcing in... more

The aim of the current study was to examine whether moral disengagement and defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with defending and reinforcing in school bullying situations in late childhood. Self-reported survey data were collected from 1060 Swedish students from 70 classrooms in 29 schools. Multilevel analysis found that greater defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with greater defending. We also found that greater moral disengagement and less (but very weakly) defender self-efficacy at individual level and less collective efficacy to stop peer aggression at classroom level were associated with greater reinforcing. The positive relationship between moral disengagement and reinforcing and the negative relationship between defender self-efficacy and reinforcing were less strong in classroom high in collecti...

Background Wild-type RD114 virus is capable of generating syncytia during its replication, and it is believed that cell-free viruses direct the fusion of neighboring cells. The RD114 envelope (Env) that mediates this fusion event is now... more

Background Wild-type RD114 virus is capable of generating syncytia during its replication, and it is believed that cell-free viruses direct the fusion of neighboring cells. The RD114 envelope (Env) that mediates this fusion event is now widely used to pseudotype retroviral and lentiviral vectors in gene therapy. Indeed, vectors pseudotyped with RD114 Env are very efficient to transfer genes into human hematopoietic cells, and they are resistant to human complement inactivation. In this study, we have tested the potential of RD114-pseudotyped vectors produced from the FLYRD18 packaging cell line to induce syncytia. Methods RD114-pseudotyped vectors produced from the FLYRD18 packaging cells were added on tumor cell lines, and the formation of syncytia was assessed by microscopy after cell fixation and methylene blue staining. The kinetics of syncytium formation was analyzed by time-lapse microscopy. Finally, the cytotoxic effect of RD114-pseudotyped vectors was measured by the MTT assay on tumor cells, and in combination with the TK/GCV strategy. Results We have found that these vectors were able to mediate cell-to-cell fusion of human tumor cell lines. A few hours after addition of the vector, cells started to aggregate to form syncytia that eventually evolved toward cell death 48 h postinfection. RD114-pseudotyped vectors were very efficient at killing human cancer cells, and they were also able to enhance dramatically the cytotoxic effect of the TK/GCV strategy. Conclusions These findings indicate that RD114-pseudotyped vectors used alone, or in combination with a suicide gene therapy approach, have great potential for the treatment of cancer.

Attenuated salmonella have been reported to be capable of both selectively growing in tumors and expressing exogenous genes for tumor-targeted therapy. As 6-methoxypurine 2′ ′ ′ ′-deoxyriboside (MoPdR) is similar to 6-methylpurine 2′ ′ ′... more

Attenuated salmonella have been reported to be capable of both selectively growing in tumors and expressing exogenous genes for tumor-targeted therapy. As 6-methoxypurine 2′ ′ ′ ′-deoxyriboside (MoPdR) is similar to 6-methylpurine 2′ ′ ′ ′-deoxyriboside in structure, we aimed to evaluate the antitumoral effect of the Escherichia coli purine nucleoside phosphorylase (ePNP) gene, using an attenuated salmonella-mediated delivery system, in combination with MoPdR. A novel mutant serovar Typhimurium (SC36) was used to carry the pEGFP-C1-ePNP vector that contains an enhanced green fluorescent protein and an ePNP gene under the control of the cytomegalovirus promoter. The function of the ePNP expression vector was confirmed in vitro using the enzymic conversion of MoPdR into methoxypurine. We also observed a high bystander effect induced by the ePNP/MoPdR system with a very low proportion (1%) of ePNP-positive cells and 5 µ µ µ µg/mL MoPdR, although the growth of parental cells was affected appreciably by MoPdR. The killing effect and increased apoptosis induced by SC36 carrying the ePNP expression vector (SC/ePNP) were detected by cytotoxicity assay and propidium iodide staining flow cytometry analysis, in combination with MoPdR. SC/ePNP was given orally to mice bearing mammary carcinomas, and its antitumor effect was evaluated. SC/ ePNP plus MoPdR significantly inhibited tumor growth by approximately 86.6-88.7% and prolonged the survival of tumorhosting mice. Our data support the view that MoPdR combined with the ePNP gene could be used in gene-directed enzyme prodrug therapy. Attenuated salmonella could be a promising strategy to improve ePNP/MoPdR bystander killing due to its preferential accumulation and anticancer activity in tumors. (Cancer Sci 2008; 99: 1172-1179) Bruce A.. A novel purine-auxotrophic mutant SC36 (his G aro A cys pur I) with a low residual virulence was gained by diethyl sulfate mutagenesis of SL3261, as previously described. Bacterial strains were routinely grown at 37°C in Luria broth (LB) or agar supplemented with kanamycin (50 µg/mL). pEGFP-C1 and pEGFP-C1-ePNP were first transformed into LB5000 using electrotransformation in cuvettes (0.2 cm electrode gap; Eppendorf) with a single pulse of 12.5 kV/cm (2.5 kV, 200 Ω, 25 µF). After amplification of the colony, the plasmids were extracted from the transferred LB5000 (3S Spin Plasmid Miniprep Kit V3.1; Shanghai Shenergy Biocolors Bioscience & Technology Co. Ltd.) then introduced into SC36 (as carried out for LB5000) to generate SC/pEGFP and SC/ePNP. Cells, cell culture, and bacterial infection. Murine mammary carcinoma 4T1 cell lines were obtained from Shanghai No.1 People's Branch Hospital (China). The cells (10 5 cells/well) were cultured in 12-well plates overnight in antibiotic-free RPMI-1640 media (Gibco BRL) in a 5% CO 2 atmosphere at 37°C. Bacteria (SC/pEGFP or SC/ePNP) were shaken in LB broth with kanamycin (50 µg/mL) overnight at 37°C to reach the late logarithmic phase of growth (OD 600 of approximately 4) and suspended in antibiotic-free media. Then 2.5 × 10 7 c.f.u. of bacteria (at a multiplicity of infection of 1:250) were directly added into 12-well plates and co-incubated with tumor cells for 3 h. Subsequently, the cells were washed three times with phosphate-buffered saline (PBS) and replenished with complete media (containing 100 U/mL penicillin and 100 µg/mL streptomycin) and further cultured for 1 or 2 days. The infected cells were collected and some of them were used to monitor the gene expression by reverse transcription (RT)-PCR (AccessQuick;

Cyberbullying incidents often occur in the presence of other bystanders. The inaction of bystanders can augment the deleterious effects of bullying on a victim. However, bystanders can intervene to stop a cyberbullying incident or offer... more

Cyberbullying incidents often occur in the presence of other bystanders. The inaction of bystanders can augment the deleterious effects of bullying on a victim. However, bystanders can intervene to stop a cyberbullying incident or offer support to the victim. Two studies were conducted to examine variables that were expected to influence the propensity of a bystander to take action in cyberbullying incidents: the number of bystanders, the anonymity of the bystander, and the closeness between the bystander and the victim. Results supported the diffusion of responsibility effect. A higher number of bystanders was negatively associated with bystander intervention. Moreover, the perceived anonymity of bystanders was negatively related to the propensity to intervene, and closeness with the victim was associated with a greater tendency to intervene and support the victim. Altogether, the results shed light on the interplay of context, relationships, and technology in the behavior of bystanders to a cyberbullying episode.

The aim of the present study was to examine to what degree different mechanisms of moral disengagement were related to age, gender, bullying, and defending among school children. Three hundred and seventy-two Swedish children ranging in... more

The aim of the present study was to examine to what degree different mechanisms of moral disengagement were related to age, gender, bullying, and defending among school children. Three hundred and seventy-two Swedish children ranging in age from 10 to 14 years completed a questionnaire. Findings revealed that boys expressed significantly higher levels of moral justification, euphemistic labeling, diffusion of responsibility, distorting consequences, and victim attribution, as compared with girls. Whereas boys bullied others significantly more often than girls, age was unrelated to bullying. Moral justification and victim attribution were the only dimensions of moral disengagement that significantly related to bullying. Furthermore, younger children and girls were more likely to defend victims. Diffusion of responsibility and victim attribution were significantly and negatively related to defending, while the other dimensions of moral disengagement were unrelated to defending.

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... more

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 grounded theory. The analysis of the student voices of being a bystander in bullying reveals a complexity in which different definition-of-situation processes are evoked (a) relations (friends and social hierarchy), (b) defining seriousness, (c) victim’s contribution to the situation, (d) social roles and intervention responsibilities, and (e) distressing emotions. There are often conflicted motives in how to act as a bystander, which could evoke moral distress among the students. Our analysis is unique in that it introduces the concept of moral distress as a process that has to be considered in order to better understand bystander actions among children The findings also indicate bystander reactions that could be associated with moral disengagement, such as not perceiving a moral obligation to intervene if the victim is defined as a non-friend (‘none of my business’), protecting the friendship with the bully, and blaming the victim.

En el siguiente trabajo de investigación para la Cátedra EL DRAMATURGO ARGENTINO Y LA TRADICIÓN (Liliana López, 2016) tomo el el texto dramático Los prójimos (1966) de Carlos Gorostiza para analizar contexto, fuentes y progresos de la... more

En el siguiente trabajo de investigación para la Cátedra EL DRAMATURGO ARGENTINO Y LA TRADICIÓN (Liliana López, 2016) tomo el el texto dramático Los prójimos (1966) de Carlos Gorostiza para analizar contexto, fuentes y progresos de la estética realista de la década del 60.

Objective: Internal whistle-blowing is known as one of the most effective methods for identifying fraud. Understanding the factors influencing the reporting of fraud according to the bystander effect can be a great help in reducing fraud.... more

Objective: Internal whistle-blowing is known as one of the most effective methods for identifying fraud. Understanding the factors influencing the reporting of fraud according to the bystander effect can be a great help in reducing fraud. This is important in this study with the aim of the pattern of factors affecting the whistle-blowing with emphasis on the bystander effect. Methods: To answer the research question, Meta-composition, content analysis, and semi-structured interviews with experts (Delphi) were used. A total of 61 articles related to the research topic include fraud, spectator, bystander effect, fraud report, whistleblowing, diffusion of responsibility, non-motivated, and disclosure of illegal activities, were analyzed and 14 experts were interviewed. Results: Analyzes show that 5 individual structures (including 19 cases and cases such as weakness of courage and fear of evaluation and judgment), interpersonal (including 4 cases and cases such as unfamiliarity with the principles of social behavior and weakness in social responsibility), moral-Cultural (including 9 cases and cases such as weakness in piety and spirituality and lack of honesty and integrity), administrative-managerial (including 12 cases and cases such as lack of legal and social support and lack of organizational transparency) and the nature of the violation (including 7 cases and cases such as The number of informed people and the uncertainty of the occurrence of violations affect the internal reporting of financial violations) because of the spectator phenomenon. Also, each structure has components, and each component affects the spectator and internal reporting of financial violations. Conclusion: In some cases, the violation can be reported to other employees, but instead of reporting, they only become spectators who have observed the violation. Spectator management allows employees to report financial violations. Violators are in front of the eyes of spectators who feel responsible for exposing the violation. This study examined this issue and showed that paying attention to the five identified structures will reduce corruption and misconduct and will protect the interests of stakeholders and the public. It also provides a platform for employees to report violations in organizations.

While leadership scholars increasingly acknowledge the influence of followers in the leadership process, less attention has been paid to their role in the destructive leadership process. Specifically, the current debate lacks a... more

While leadership scholars increasingly acknowledge the influence of followers in the leadership process, less attention has been paid to their role in the destructive leadership process. Specifically, the current debate lacks a broad-based understanding of different susceptible follower types that synthesizes related research across academic domains. Expanding on Padilla, Hogan, and Kaiser's (2007) toxic triangle model of destructive leadership, we integrate research and theory across various academic literatures to derive a cohesive taxonomy of vulnerable followers that we call the susceptible circle. We describe the core characteristics of each follower type, drawing on Barbuto's (2000) theory of follower compliance to highlight the psychological processes that motivate each follower to comply with destructive leaders. We then conclude by discussing theoretical and practical implications, as well as avenues for future research.

With reference to social-ecological, self-determination, attributional, and social cognitive theories, the current study examined whether gender, age, altruistic motivation to defend victims, and tendency to blame the victims, at the... more

With reference to social-ecological, self-determination, attributional, and social cognitive theories, the current study examined whether gender, age, altruistic motivation to defend victims, and tendency to blame the victims, at the individual level, and the prevalence of reinforcing and defending, at the classroom level, were associated with bullying. A sample of 901 Swedish students (9–13 years old, M = 11.00, SD = .83) from 43 classrooms filled out a questionnaire. Multilevel regression analyses revealed that the perpetration of bullying was positively associated with the prevalence of reinforcing at the classroom level and blaming the victims at the individual level, whereas it was negatively associated with altruistic motivation to defend victims of bullying at the individual level. Furthermore, students with high altruistic motivation to defend victims of bullying were less inclined to bully, independent of the classroom level of reinforcing. The current study suggests that bullying prevention and intervention programs should: explicitly target bystander behaviors, in particular to reduce the prevalence of reinforcing bullying; include efforts to strengthen altruistic self-concept and motivation to defend victims; and prevent, challenge, and counteract tendencies among students to blame the victim.

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... more

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 bystander behaviors in bullying situations. Three hundred and forty-seven teenagers completed a bullying survey. Findings indicated that compared with boys, girls expressed higher basic moral sensitivity in bullying, lower defender self-efficacy and moral disengagement in bullying. Results from the SEM showed that basic moral sensitivity in bullying was negatively related to pro-bully behavior and positively related to outsider and defender behavior, mediated by moral disengagement in bullying, which in turn was positively related to pro-bully behavior and negatively related to outsider and defender behavior. What differed in the relations between outsider and defender behaviors was the degree of defender self-efficacy.

This study examined whether students' bystander behaviours in peer victimisation were associated with individual (IMD) and classroom collective moral disengagement (CMD). Self-report survey data were analysed from 1577 Swedish students in... more

This study examined whether students' bystander behaviours in peer victimisation were associated with individual (IMD) and classroom collective moral disengagement (CMD). Self-report survey data were analysed from 1577 Swedish students in fifth grade. Multilevel analyses revealed that, when witnessing peer victimisation, students more often sided with the victimisers if they belonged to classrooms high in CMD, especially if they simultaneously were high in IMD. Furthermore, staying passive was associated with higher levels of IMD and CMD, whereas defending the victims was associated with lower levels of IMD and CMD. Taken together, our findings suggest that moral disengagement beliefs both at the individual and at the classroom-level contribute to explain variability in students' bystander behaviours, which has potential implications for prevention and intervention work.

The aim of the current study was to examine whether moral disengagement and defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with defending and reinforcing in... more

The aim of the current study was to examine whether moral disengagement and defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with defending and reinforcing in school bullying situations in late childhood. Self-reported survey data were collected from 1060 Swedish students from 70 classrooms in 29 schools. Multilevel analysis found that greater defender self-efficacy at individual level and collective efficacy to stop peer aggression at classroom level were associated with greater defending. We also found that greater moral disengagement and less (but very weakly) defender self-efficacy at individual level and less collective efficacy to stop peer aggression at classroom level were associated with greater reinforcing. The positive relationship between moral disengagement and reinforcing and the negative relationship between defender self-efficacy and reinforcing were less strong in classroom high in collective efficacy to stop aggression.

Bystander behavior in bullying has received increasing attention in the literature, but it is seldom grounded in a strong theoretical context and rarely draws from multiple disciplines. The current article proposes how theory in mass... more

Bystander behavior in bullying has received increasing attention in the literature, but it is seldom grounded in a strong theoretical context and rarely draws from multiple disciplines. The current article proposes how theory in mass communication can aid research efforts seeking to better understand and prevent bullying through bystander intervention. This article first provides an overview of the research on bystanders in bullying and uses Latané and Darley's (The unresponsive bystander: why doesn't he help? Prentice Hall, Englewood Cliffs, 1970) classic bystander intervention model as an organizing framework. Next, mass communication theory, with its focus on the strategic use of messaging to affect attitudes and behaviors, is reviewed. Theory and research in communication relevant to the prevention of bullying is then discussed, with particular attention to the bystander intervention model. The article concludes with recommendations for how future research and interventions grounded in communication and psychology may advance our understanding and encouragement of adolescent bystander intervention behavior in bullying.

Radiation-induced adaptive response belongs to the group of non-targeted effects that do not require direct exposure of the cell nucleus by radiation. It is described as the reduced damaging effect of a challenging radiation dose when... more

Radiation-induced adaptive response belongs to the group of non-targeted effects that do not require direct exposure of the cell nucleus by radiation. It is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. Adaptive responses have been observed in vitro and in vivo using various indicators of cellular damage, such as cell lethality, chromosomal aberrations, mutation induction, radiosensitivity, and DNA repair. Adaptive response can be divided into three successive biological phenomena, the intracellular response, the extracellular signal, and the maintenance. The intracellular response leading to adaptation of a single cell is a complex biological process including induction or suppression of gene groups. An extracellular signal, the nature of which is unknown, may be sent by the affected cell to neighbouring cells causing them to adapt as well. This occurs either by a release of diffusible signalling molecules or by gap-junction intercellular communication. Adaptive response can be maintained for periods ranging from of a few hours to several months. Constantly increased levels of reactive oxygen species (ROS) or nitric oxide (NO) have been observed in adapted cells and both factors may play a role in the maintenance process. Although adaptive response seems to function by an on/off principle, it is a phenomenon showing a high degree of inter- and intraindividual variability. It remains to be seen to what extent adaptive response is functional in humans at relevant dose and dose-rate exposures. A better understanding of adaptive response and other non-targeted effects is needed before they can be confirmed as risk estimate factors for the human population at low levels of ionising radiation.

The aim of this study was to examine how different bystander roles in peer victimisation situations relate to moral disengagement, defender self-efficacy, and student-teacher relationship quality. Self-reported survey data were collected... more

The aim of this study was to examine how different bystander roles in peer victimisation situations relate to moral disengagement, defender self-efficacy, and student-teacher relationship quality. Self-reported survey data were collected from 333 middle and junior high school students (10–15 years of age) from four schools in Sweden. Random intercept model analyses of factor scores revealed that, when witnessing peer victimisation, students high in moral disengagement and low in defender self-efficacy were more inclined to act as reinforcers or outsiders, and that students high in defender self-efficacy and student-teacher relationship quality were more inclined to act as defenders. Furthermore, exam- ining these relationships within and between classes revealed that reinforcer and outsider behaviours were more common among students who, compared to their classmates, were higher in moral disengagement and lower in defender self-efficacy, whereas defending was more common among students who, compared to their classmates, were higher in defender self-efficacy. The results enrich the knowledge of factors related to different bystander behaviours, which has potential implications for prevention and intervention work.

Research has shown that bystanders more often fail to or are slower to help a victim in emergency when there are other bystanders than when there are not. The study presented in this paper is a qualitative case study with a focus on... more

Research has shown that bystanders more often fail to or are slower to help a victim in emergency when there are other bystanders than when there are not. The study presented in this paper is a qualitative case study with a focus on students’ own reasons why they do not help a classmate in emergency when there are other children witnessing the emergency situation in the real-life classroom case studied. Grounded theory methods were used to analyse the data. The individual conversations with the students indicated a variety of definitions of the specific distress situation when they recalled and talked about the classroom incident. During the process of the analysis seven concepts of definitions associated with passive or non-intervention bystander behaviour were constructed and grounded in the empirical material: trivialisation, dissociation, embarrassment association, busy working priority, compliance with a competitive norm, audience modelling, and responsibility transfer. Relations between these concepts of definitions were also analysed. However, this study is a first step and a first report from an ongoing study about school children as helper and bystander.

Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with... more

Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease,we found that treatment with single RTL could reverse EAE as long as targeted Tcells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS.

It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked... more

It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiationinduced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low-and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / r e v i e w s m r C o m m u n i t y a d d r e s s : w w w . e l s e v i e r . c o m / l o c a t e / m u t r e s 1383-5742/$ -see front matter ß

Human skin is a stratified organ frequently exposed to sun-generated ultraviolet radiation (UVR), which is considered one of the major factors responsible for DNA damage. Such damage can be direct, through interactions of DNA with UV... more

Human skin is a stratified organ frequently exposed to sun-generated ultraviolet radiation (UVR), which is considered one of the major factors responsible for DNA damage. Such damage can be direct, through interactions of DNA with UV photons, or indirect, mainly through enhanced production of reactive oxygen species that introduce oxidative changes to the DNA. Oxidative stress and DNA damage also associate with profound changes at the cellular and molecular level involving several cell cycle and signal transduction factors responsible for DNA repair or irreversible changes linked to ageing. Crucially, some of these factors constitute part of the signalling known for the induction of biological changes in non-irradiated, neighbouring cells and defined as the bystander effect. Network interactions with a number of natural compounds, based on their known activity towards these biomarkers in the skin, reveal the capacity to inhibit both the bystander signalling and cell cycle/DNA damage molecules while increasing expression of the anti-oxidant enzymes. Based on this information , we discuss the likely polypharmacology applications of the natural compounds and next-generation screening technologies in improving the anti-oxidant and DNA repair capacities of the skin.

Abscopal effect Immune system Heat shock protein 70 a b s t r a c t Considerable progress has recently been achieved in the understanding of molecular mechanisms involved in cellular radiation responses and radiation mediated... more

Abscopal effect Immune system Heat shock protein 70 a b s t r a c t Considerable progress has recently been achieved in the understanding of molecular mechanisms involved in cellular radiation responses and radiation mediated microenvironmental communication.

Our understanding of how radiation kills normal and tumour cells has been based on an intimate knowledge of the direct induction of DNA damage and its cellular consequences. What has become clear is that, as well as responses to direct... more

Our understanding of how radiation kills normal and tumour cells has been based on an intimate knowledge of the direct induction of DNA damage and its cellular consequences. What has become clear is that, as well as responses to direct DNA damage, cell-cell signalling -known as the bystander effect -mediated through gap junctions and inflammatory responses may have an important role in the response of cells and tissues to radiation exposure and also chemotherapy agents. This Review outlines the key aspects of radiation-induced intercellular signalling and assesses its relevance for existing and future radiation-based therapies.

Significance: Ionizing radiation (IR) can induce a wide range of unique deoxyribonucleic acid (DNA) lesions due to the spatiotemporal correlation of the ionization produced. Of these, DNA double strand breaks (DSBs) play a key role.... more

Significance: Ionizing radiation (IR) can induce a wide range of unique deoxyribonucleic acid (DNA) lesions due to the spatiotemporal correlation of the ionization produced. Of these, DNA double strand breaks (DSBs) play a key role. Complex mechanisms and sophisticated pathways are available within cells to restore the integrity and sequence of the damaged DNA molecules. Recent Advances: Here we review the main aspects of the DNA DSB repair mechanisms with emphasis on the molecular pathways, radiation-induced lesions, and their significance for cellular processes. Critical Issues: Although the main characteristics and proteins involved in the two DNA DSB repair processes present in eukaryotic cells (homologous recombination and nonhomologous end-joining) are reasonably well established, there are still uncertainties regarding the primary sensing event and their dependency on the complexity, location, and time of the damage. Interactions and overlaps between the different pathways play a critical role in defining the repair efficiency and determining the cellular functional behavior due to unrepaired/miss-repaired DNA lesions. The repair pathways involved in repairing lesions induced by soluble factors released from directly irradiated cells may also differ from the established response mechanisms. Future Directions: An improved understanding of the molecular pathways involved in sensing and repairing damaged DNA molecules and the role of DSBs is crucial for the development of novel classes of drugs to treat human diseases and to exploit characteristics of IR and alterations in tumor cells for successful radiotherapy applications.

Pulling from in-depth interviews with school administrators, counselors, security and police officers, and teachers directly involved in thwarting rampage attacks at 11 Northeastern schools, this study considers the extent to which... more

Pulling from in-depth interviews with school administrators, counselors, security and police officers, and teachers directly involved in thwarting rampage attacks at 11 Northeastern schools, this study considers the extent to which students have broken through a ''code of silence,'' discouraging them from informing on their peers. While findings support prior research indicating the vital preventative role of students' coming forward with information about threats, close scrutiny of averted incidents reveals that scholars and educational practitioners have overestimated the extent to which the student code of silence has diminished post-Columbine. Even in these successfully averted incidents, numerous students exposed to threats still did not come forward; those who did were rarely close associates or confidants of accused students; and some who did ultimately come forward did so as a result of being personally threatened or in order to deflect blame away from themselves, rather than out of altruistic concern for others.

The purpose of this study was to investigate and generate a grounded theory on how and why students behave as they do in school situations in which they witness another student in distress. Fieldwork and interviews were conducted in 2... more

The purpose of this study was to investigate and generate a grounded theory on how and why students behave as they do in school situations in which they witness another student in distress. Fieldwork and interviews were conducted in 2 Swedish elementary schools and guided by a grounded theory approach. The study resulted in a grounded theory of moral frames in bystander situations in school. In this study, 5 main moral frames of school have been identified: (a) the moral construction of the good student, (b) institutionalized moral disengagement, (c) tribe caring, (d) gentle caring-girl morality, and (e) social-hierarchy-dependent morality. The study highlights how moral action is generally inhibited by the conformity fostered in school settings and by moral dilemmas constructed by the moral frames. A revised model of bystander behavior adapted to the school context is also presented.

Radiation induced non-targeted effects have been widely investigated in the last two decades for their potential impact on low dose radiation risk. In this paper we will give an overview of the most relevant aspects related to these... more

Radiation induced non-targeted effects have been widely investigated in the last two decades for their potential impact on low dose radiation risk. In this paper we will give an overview of the most relevant aspects related to these effects, starting from the definition of the low dose scenarios. We will underline the role of radiation quality, both in terms of mechanisms of interaction with the biological matter and for the importance of charged particles as powerful tools for low dose effects investigation. We will focus on cell communication, representing a common feature of non-targeted effects, giving also an overview of cancer models that have explicitly considered such effects.

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... more

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.

In planning treatment for each new patient, radiation oncologists pay attention to the aspects that they control. Thus their attention is usually focused on volume and dose. The dilemma for the physician is how to protract the treatment... more

In planning treatment for each new patient, radiation oncologists pay attention to the aspects that they control. Thus their attention is usually focused on volume and dose. The dilemma for the physician is how to protract the treatment in a way that maximizes control of the tumor and minimizes normal tissue injury. The initial radiation-induced damage to DNA may be a biological indicator of the quantity of energy transferred to the DNA. However, until now the biophysical models proposed cannot explain either the early or the late adverse effects of radiation, and a more general theory appears to be required. The bystander component of tumor cell death after radiotherapy measured in many experimental works highlights the importance of confirming these observations in a clinical situation.

These experiments were designed to look at the cellular effects in key organs in Atlantic salmon (Salmo salar) after exposure in vivo to radiation and subtoxic levels of aluminum (Al) and cadmium (Cd), alone or in combination. Salmon (25... more

These experiments were designed to look at the cellular effects in key organs in Atlantic salmon (Salmo salar) after exposure in vivo to radiation and subtoxic levels of aluminum (Al) and cadmium (Cd), alone or in combination. Salmon (25 g) were exposed to a single 0.5 Gy dose of g-irradiation in water containing Cd, Al or Cd þ Al. Three fish per group were sacrificed after 1 h and the liver, pronephros, fin and gill of each was dissected. Small explants of each tissue were set up. After 2 days, the culture medium was harvested and filtered then placed on a reporter cell line for determination of stress signal activity (bystander effects). Radiation in combination with Cd and/or Al, caused bystander effects in tissues harvested from in vivo exposed salmon. The effects vary between different organs and are not consistently additive or synergistic for a given treatment. Tissue type appears to be critical. Liver cultures produce a toxic factor which is lethal to reporter cells, and therefore no liver data could be obtained. It is hoped that this stress signal response will prove to be a useful indicator of environmental stress in species inhabiting aquatic ecosystems.

The time course of cytotoxicity induction and the bystander effect of the rabbit cytochrome P450 4B1 ( cyp4B1 ) / 4 -ipomeanol ( 4 -IM ) or 2 -aminoanthracene ( 2 -AA ) pharmacogene therapy systems were investigated and compared with the... more

The time course of cytotoxicity induction and the bystander effect of the rabbit cytochrome P450 4B1 ( cyp4B1 ) / 4 -ipomeanol ( 4 -IM ) or 2 -aminoanthracene ( 2 -AA ) pharmacogene therapy systems were investigated and compared with the herpes simplex virus type 1 thymidine kinase / ganciclovir ( HSV -tk / GCV ) system. Experiments were performed in rat 9L gliosarcoma cells stably expressing cyp4B1 ( 9L -4B1 ), HSV -tk ( 9L -tk ), or their egfp ( enhanced green fluorescent protein ) fusion genes. Cyp4B1 -mediated activation of 2 -AA showed a high cell killing efficiency within only 48 hours with an onset after already 15 minutes of prodrug exposure. Residual 9L -4B1 cells were mostly damaged sublethally upon 2 -AA treatment showing an S phase arrest by cell cycle analysis. 4 -IM treatment of 9L -4B1 cells generated an overall weaker cell killing, especially after prodrug exposure times of less than 48 hours. Residual cells surviving 4 -IM treatment showed a G2 / M arrest and restarted proliferation after prodrug treatment was stopped. HSV -tk / GCV pharmacogene therapy resulted in a slower cytotoxicity induction than cyp4B1 / 2 -AA treatment with a significantly lower cell killing efficiency after 24 and 48 hours. HSV -tk / GCV -mediated cytotoxicity was widely similar to the cytotoxicity induced by cyp4B1 / 4 -IM with the exception of a continuous 48 -hour prodrug exposure where 4 -IM treatment showed a significantly higher cell killing rate. Cells surviving HSV -tk / GCV suicide gene therapy were not viable and showed an S -phase arrest. Whereas HSV -tk / GCV induced a strong bystander effect, only moderate bystander cell death depending on cell -to -cell contact was demonstrated in 9L / 9L -4B1 cocultures upon 2 -AA treatment and was even absent with 4 -IM, thereby contrasting with earlier reports. The absence of a strong bystander effect may limit, on one hand, the overall utility of the cyp4B1 systems for cancer gene therapy. On the other hand, the weak bystander effect together with the fast induction of cytotoxicity may provide marked advantages for the use of the cyp4B1 systems as biosafety enhancers for gene marking or replacement studies and donor lymphocyte infusions after allogeneic bone marrow transplantation.

The goal of the present paper is to construct a formal explication of the pluralistic ignorance explanation of the bystander effect. The social dynamics leading to inaction is presented, decomposed, and modeled using dynamic epistemic... more

The goal of the present paper is to construct a formal explication of the pluralistic ignorance explanation of the bystander effect. The social dynamics leading to inaction is presented, decomposed, and modeled using dynamic epistemic logic augmented with ‘transition rules’ able to characterize agent behavior. Three agent types are defined: First Responders who intervene given belief of accident; City Dwellers, capturing ‘apathetic urban residents’ and Hesitators, who observe others when in doubt, basing subsequent decision on social proof. It is shown how groups of the latter may end in a state of pluralistic ignorance leading to inaction. Sequential models for each agent type are specified, and their results compared to empirical studies. It is concluded that only the Hesitator model produces reasonable results.

Residual DNA DSB damage contributes to late normal tissue toxicity. Here we studied the variations in DNA DSB damage processing along and in the surroundings of therapeutic proton beams in normal human cells using the 53BP1 foci assay.... more

Residual DNA DSB damage contributes to late normal tissue toxicity. Here we studied the variations in DNA DSB damage processing along and in the surroundings of therapeutic proton beams in normal human cells using the 53BP1 foci assay. Our results indicate a significant induction of complex DNA damage at the distal end of the Bragg peak. Variation in the DNA repair efficiency is important Purpose: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. Methods and Materials: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, and distal positions of SOBP and the entrance and peak position for the pristine beam. Results: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci.

The Marange diamond mines in Zimbabwe have been a source of conflict, abuse and abandonment of social responsibility since alluvial diamonds were discovered there in 2006. Much attention is given to the Kimberley Process which was set up... more

The Marange diamond mines in Zimbabwe have been a source of conflict, abuse and abandonment of social responsibility since alluvial diamonds were discovered there in 2006. Much attention is given to the Kimberley Process which was set up to monitor conflict diamonds. But the Kimberley Process' narrow definition of conflict diamonds, contingent upon international collaboration, has limited its ability to reduce abuses and corruption in the Marange Mines. The present paper draws a connection between the social psychological phenomenon of the bystander effect and the present state of management for the diamond supply chain in Marange and beyond. Social psychological interventions to address the problems are suggested. It is understood that the complexities of the diamond trade require more than one approach to address potential issues. The role of diffusion of responsibility and culture are also proposed as subjects for future study in the overall field of corporate social responsibility.

Over the past 20 or so years experimental evidence, which questions the fundamentals of some 50 years standing, of both biology and radiobiology has accrued. In order to accommodate this new evidence within a framework that encompasses... more

Over the past 20 or so years experimental evidence, which questions the fundamentals of some 50 years standing, of both biology and radiobiology has accrued. In order to accommodate this new evidence within a framework that encompasses existing knowledge, attention has to be paid to the organisational or epigenetic, features of the cell. In recent years the high dimensional dynamic attractor has emerged as a potential organisational or regulatory agent that represents phenotype. It is argued here that its limited robustness provides a modus operandi to account for stress induced genomic instability.When radiation deposition events act to overcome the robustness of a normal or “home” attractor in the cell of an established species and cause a transition to a variant attractor or phenotype, the consequences are unrelated to any specific molecular damage to the genomic DNA. Rather they correspond to the loss of evolutionarily acquired stability (genotypic replicative integrity) and robustness. Such processes are termed type B events and give rise to a separate category of effects and risk to those associated with the conventional effects of radiation, type A effects. How type B risks might be assessed is discussed.

Hypoxia contributes to resistance of tumors to some cytotoxic drugs and to radiotherapy, but can in principle be exploited with hypoxia-activated prodrugs (HAP). HAP in clinical development fall into two broad groups. Class I HAP (like... more

Hypoxia contributes to resistance of tumors to some cytotoxic drugs and to radiotherapy, but can in principle be exploited with hypoxia-activated prodrugs (HAP). HAP in clinical development fall into two broad groups. Class I HAP (like the benzotriazine N-oxides tirapazamine and SN30000), are activated under relatively mild hypoxia. In contrast, Class II HAP (such as the nitro compounds PR-104A or TH-302) are maximally activated only under extreme hypoxia, but their active metabolites (effectors) diffuse to cells at intermediate O2 and thus also eliminate moderately hypoxic cells. Here, we use a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) model to compare these two strategies and to identify the features required in an optimal Class II HAP. The model uses a Green's function approach to calculate spatial and longitudinal gradients of O2, prodrug, and effector concentrations, and resulting killing in a digitized 3D tumor microregion to estimate activity as monoth...

The sequence of events involved in maintenance of homeostasis must encompass mechanisms within single cells as well as interactions between cells within a population. To investigate the interaction among these inter-and intracellular... more

The sequence of events involved in maintenance of homeostasis must encompass mechanisms within single cells as well as interactions between cells within a population. To investigate the interaction among these inter-and intracellular mechanisms, disruption of homeostasis by serum deprivation was performed in WB-F344, a normal diploid epithelial cell line.

Objective. To examine blood samples from survivors of the Chernobyl accident for evidence of persistent bystander factors or clastogenic factors and to look at the ability of melanin and melatonin, which are radioprotective agents capable... more

Objective. To examine blood samples from survivors of the Chernobyl accident for evidence of persistent bystander factors or clastogenic factors and to look at the ability of melanin and melatonin, which are radioprotective agents capable of preventing bystander effects in cell culture to prevent toxic effects. Materials and Methods. Serum was extracted from blood samples of control and test groups and added to human immortalized reporter cells, used in our laboratories for identification of bystander effects. These were then analyzed for evidence of micronucleus formation and viability.

The major adverse consequences of radiation exposures are attributed to DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes. However, the dogma that genetic alterations are restricted to... more

The major adverse consequences of radiation exposures are attributed to DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes. However, the dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that are the descendants of irradiated cells either directly or via media transfer (radiation-induced genomic instability) or in cells that have communicated with irradiated cells (radiation-induced bystander effects). Radiation-induced genomic instability is characterized by a number of delayed responses including chromosomal abnormalities, gene mutations and cell death. Bystander effects include increases or decreases in damage-inducible and stress-related proteins, increases or decreases in reactive oxygen and nitrogen species, cell death or cell proliferation...

The aim of this study was to examine how different bystander roles in peer victimisation situations relate to moral disengagement, defender self-efficacy, and student-teacher relationship quality. Self-reported survey data were collected... more

The aim of this study was to examine how different bystander roles in peer victimisation situations relate to moral disengagement, defender self-efficacy, and student-teacher relationship quality. Self-reported survey data were collected from 333 middle and junior high school students (10–15 years of age) from four schools in Sweden. Random intercept model analyses of factor scores revealed that, when witnessing peer victimisation, students high in moral disengagement and low in defender self-efficacy were more inclined to act as reinforcers or outsiders, and that students high in defender self-efficacy and student-teacher relationship quality were more inclined to act as defenders. Furthermore, examining these relationships within and between classes revealed that reinforcer and outsider behaviours were more common among students who, compared to their classmates, were higher in moral disengagement and lower in defender self-efficacy, whereas defending was more common among students who, compared to their classmates, were higher in defender self-efficacy. The results enrich the knowledge of factors related to different bystander behaviours, which has potential implications for prevention and intervention work.

The efficacy of HSV-TK7ganciclovir gene therapy largely relies on the bystander effect, i.e. the ability of transfected cells to kill the adjacent, untrasfected cells. This mechanism itself depends chiefly on the transfer via gap... more

The efficacy of HSV-TK7ganciclovir gene therapy largely relies on the bystander effect, i.e. the ability of transfected cells to kill the adjacent, untrasfected cells. This mechanism itself depends chiefly on the transfer via gap junctions of phosphorylated ganciclovir between cells, and is often deficient in glioblastomas. In this report, we demonstrate that n-butyrate markedly enhances the gap junction inter cellular communication of GJIC-deficient glioma cells, and significantly increases the bystander effect in such cells.

Two studies tested whether individual differences in the tendency to experience embarrassment could predict interpersonal helping behavior (informing another individual about a correctible flaw). In Study 1, 84 participants were given a... more

Two studies tested whether individual differences in the tendency to experience embarrassment could predict interpersonal helping behavior (informing another individual about a correctible flaw). In Study 1, 84 participants were given a chance to help an experimenter by telling her that she had ink on her face. Some knew she had an interview immediately following the experiment; some did not. Some participants were there with a confederate; some were alone. The presence of the confederate or of the interview predicted (negatively and positively, respectively) whether the participant would point out the ink. Among those who pointed out the ink, individuals higher in embarrassability were slower to help. In Study 2, participants reported on real-life interactions with others who had a temporary flaw (e.g., food in their teeth). Conceptually replicating Study 1, participants higher in embarrassability were less likely to point out the flaw. These studies suggest that fear of embarrassment is a strong inhibitory factor in social helping situations, and that personality factors can predict who will be inhibited from helping.

Abstract Because new members are important sources of knowledge to online knowledge communities, it is important to retain them after their initial interactions with the community. With a large-scale behavioral dataset collected from a... more

Abstract Because new members are important sources of knowledge to online knowledge communities, it is important to retain them after their initial interactions with the community. With a large-scale behavioral dataset collected from a leading online Question and Answer community for programmers, Stack Overflow, we investigated how the community's knowledge responses and social responses to newcomers' questions affected their subsequent likelihood of knowledge contribution (answering others' questions) and knowledge seeking (asking more questions). Contrary to the theory of reciprocity, and in line with predictions by the bystander effect, we found that receiving high quality answers negatively influenced new knowledge seekers' future likelihood of knowledge contribution. Consistent with the social exchange theory, receiving high quality answers positively affected newcomers' future knowledge seeking behaviors. Social responses (votes to the new members' questions) were found to have strong positive effects on both newcomers' future knowledge contribution and seeking behaviors.