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Sample records for cooperatively promote regulatory

  1. Network modularity promotes cooperation.

    Science.gov (United States)

    Marcoux, Marianne; Lusseau, David

    2013-05-07

    Cooperation in animals and humans is widely observed even if evolutionary biology theories predict the evolution of selfish individuals. Previous game theory models have shown that cooperation can evolve when the game takes place in a structured population such as a social network because it limits interactions between individuals. Modularity, the natural division of a network into groups, is a key characteristic of all social networks but the influence of this crucial social feature on the evolution of cooperation has never been investigated. Here, we provide novel pieces of evidence that network modularity promotes the evolution of cooperation in 2-person prisoner's dilemma games. By simulating games on social networks of different structures, we show that modularity shapes interactions between individuals favouring the evolution of cooperation. Modularity provides a simple mechanism for the evolution of cooperation without having to invoke complicated mechanisms such as reputation or punishment, or requiring genetic similarity among individuals. Thus, cooperation can evolve over wider social contexts than previously reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. 21 CFR 26.49 - Regulatory cooperation.

    Science.gov (United States)

    2010-04-01

    ... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY Specific Sector Provisions for Medical Devices § 26.49 Regulatory cooperation. (a) The parties and...

  3. Transatlantic Regulatory Cooperation: Background and Analysis

    Science.gov (United States)

    2009-08-24

    regulatory cooperation must deal with a number of key differences between the United States and EU concerning approaches to regulation. Key differences bear ...U.S. companies.51 2. Irrespective of annual summits, the TEP, by some accounts, went into hibernation from 1998 to 2004. Despite the many

  4. Reciprocity Outperforms Conformity to Promote Cooperation.

    Science.gov (United States)

    Romano, Angelo; Balliet, Daniel

    2017-10-01

    Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants' cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one's reputation-a finding that supports a reciprocity framework.

  5. Benevolent characteristics promote cooperative behaviour among humans.

    Science.gov (United States)

    Capraro, Valerio; Smyth, Conor; Mylona, Kalliopi; Niblo, Graham A

    2014-01-01

    Cooperation is fundamental to the evolution of human society. We regularly observe cooperative behaviour in everyday life and in controlled experiments with anonymous people, even though standard economic models predict that they should deviate from the collective interest and act so as to maximise their own individual payoff. However, there is typically heterogeneity across subjects: some may cooperate, while others may not. Since individual factors promoting cooperation could be used by institutions to indirectly prime cooperation, this heterogeneity raises the important question of who these cooperators are. We have conducted a series of experiments to study whether benevolence, defined as a unilateral act of paying a cost to increase the welfare of someone else beyond one's own, is related to cooperation in a subsequent one-shot anonymous Prisoner's dilemma. Contrary to the predictions of the widely used inequity aversion models, we find that benevolence does exist and a large majority of people behave this way. We also find benevolence to be correlated with cooperative behaviour. Finally, we show a causal link between benevolence and cooperation: priming people to think positively about benevolent behaviour makes them significantly more cooperative than priming them to think malevolently. Thus benevolent people exist and cooperate more.

  6. Social diversity promotes cooperation in spatial multigames

    Science.gov (United States)

    Qin, Jiahu; Chen, Yaming; Kang, Yu; Perc, Matjaž

    2017-04-01

    Social diversity is omnipresent in the modern world. Here we introduce this diversity into spatial multigames and study its impact on the evolution of cooperation. Multigames are characterized by two or more different social dilemmas being contested among players in the population. When a fraction of players plays the prisoner's dilemma game while the remainder plays the snowdrift game cooperation becomes a difficult proposition. We show that social diversity, determined by the payoff scaling factors from the uniform, exponential or power-law distribution, significantly promotes cooperation. In particular, the stronger the social diversity, the more widespread cooperative behavior becomes. Monte Carlo simulations on the square lattice reveal that a power-law distribution of social diversity is in fact optimal for socially favorable states, thus resonating with findings previously reported for single social dilemmas. We also show that the same promotion mechanism works in time-varying environments, thus further generalizing the important role of social diversity for cooperation in social dilemmas.

  7. Gossip and ostracism promote cooperation in groups.

    Science.gov (United States)

    Feinberg, Matthew; Willer, Robb; Schultz, Michael

    2014-03-01

    The widespread existence of cooperation is difficult to explain because individuals face strong incentives to exploit the cooperative tendencies of others. In the research reported here, we examined how the spread of reputational information through gossip promotes cooperation in mixed-motive settings. Results showed that individuals readily communicated reputational information about others, and recipients used this information to selectively interact with cooperative individuals and ostracize those who had behaved selfishly, which enabled group members to contribute to the public good with reduced threat of exploitation. Additionally, ostracized individuals responded to exclusion by subsequently cooperating at levels comparable to those who were not ostracized. These results suggest that the spread of reputational information through gossip can mitigate egoistic behavior by facilitating partner selection, thereby helping to solve the problem of cooperation even in noniterated interactions.

  8. Cooperative binding of transcription factors promotes bimodal gene expression response.

    Directory of Open Access Journals (Sweden)

    Pablo S Gutierrez

    Full Text Available In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is the first report to show that the cooperative binding of transcription factors to DNA promotes the "all-or-none" phenomenon observed in eukaryotic systems. In addition, we confirm that gene expression fluctuation levels associated with one of two cooperative binding mechanism never exceed the fluctuation levels of the other.

  9. Inducing Peer Pressure to Promote Cooperation

    OpenAIRE

    Ankur Mani; Iyad Rahwan; Alex Pentland

    2013-01-01

    Cooperation in a large society of self-interested individuals is notoriously difficult to achieve when the externality of one individual's action is spread thin and wide on the whole society. This leads to the ‘tragedy of the commons’ in which rational action will ultimately make everyone worse-off. Traditional policies to promote cooperation involve Pigouvian taxation or subsidies that make individuals internalize the externality they incur. We introduce a new approach to achieving global co...

  10. Cooperation goals, regulatory focus, and their combined effects on creativity

    NARCIS (Netherlands)

    Bittner, Jenny; Bruena, Mareen; Rietzschel, Eric F.

    2016-01-01

    This study examined the co-activation of cooperation versus competition goals with regulatory focus, and tested whether the combined effects on creativity are interactive or additive. An experiment with 192 adults showed two main effects, such that participants with a cooperation goal and a

  11. Inducing Peer Pressure to Promote Cooperation

    Science.gov (United States)

    Mani, Ankur; Rahwan, Iyad; Pentland, Alex

    2013-04-01

    Cooperation in a large society of self-interested individuals is notoriously difficult to achieve when the externality of one individual's action is spread thin and wide on the whole society. This leads to the `tragedy of the commons' in which rational action will ultimately make everyone worse-off. Traditional policies to promote cooperation involve Pigouvian taxation or subsidies that make individuals internalize the externality they incur. We introduce a new approach to achieving global cooperation by localizing externalities to one's peers in a social network, thus leveraging the power of peer-pressure to regulate behavior. The mechanism relies on a joint model of externalities and peer-pressure. Surprisingly, this mechanism can require a lower budget to operate than the Pigouvian mechanism, even when accounting for the social cost of peer pressure. Even when the available budget is very low, the social mechanisms achieve greater improvement in the outcome.

  12. Single promoters as regulatory network motifs

    Science.gov (United States)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  13. Regulatory Promotion of Emergent CCS Technology

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Lincoln; Uchitel, Kirsten; Johnson, David

    2014-01-01

    Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensive regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.

  14. A Cooperative Escherichia coli Aspartate Transcarbamoylase without Regulatory Subunits

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, K.; Kantrowitz, E

    2010-01-01

    Here we report the isolation, kinetic characterization, and X-ray structure determination of a cooperative Escherichia coli aspartate transcarbamoylase (ATCase) without regulatory subunits. The native ATCase holoenzyme consists of six catalytic chains organized as two trimers bridged noncovalently by six regulatory chains organized as three dimers, c{sub 6}r{sub 6}. Dissociation of the native holoenzyme produces catalytically active trimers, c{sub 3}, and nucleotide-binding regulatory dimers, r{sub 2}. By introducing specific disulfide bonds linking the catalytic chains from the upper trimer site specifically to their corresponding chains in the lower trimer prior to dissociation, a new catalytic unit, c{sub 6}, was isolated consisting of two catalytic trimers linked by disulfide bonds. Not only does the c{sub 6} species display enhanced enzymatic activity compared to the wild-type enzyme, but the disulfide bonds also impart homotropic cooperativity, never observed in the wild-type c3. The c{sub 6} ATCase was crystallized in the presence of phosphate and its X-ray structure determined to 2.10 {angstrom} resolution. The structure of c{sub 6} ATCase liganded with phosphate exists in a nearly identical conformation as other R-state structures with similar values calculated for the vertical separation and planar angles. The disulfide bonds linking upper and lower catalytic trimers predispose the active site into a more active conformation by locking the 240s loop into the position characteristic of the high-affinity R state. Furthermore, the elimination of the structural constraints imposed by the regulatory subunits within the holoenzyme provides increased flexibility to the c{sub 6} enzyme, enhancing its activity over the wild-type holoenzyme (c{sub 6}r{sub 6}) and c{sub 3}. The covalent linkage between upper and lower catalytic trimers restores homotropic cooperativity so that a binding event at one or so active sites stimulates binding at the other sites. Reduction

  15. Using Cooperative Structures to Promote Deep Learning

    Science.gov (United States)

    Millis, Barbara J.

    2014-01-01

    The author explores concrete ways to help students learn more and have fun doing it while they support each other's learning. The article specifically shows the relationships between cooperative learning and deep learning. Readers will become familiar with the tenets of cooperative learning and its power to enhance learning--even more so when…

  16. Character displacement promotes cooperation in bacterial biofilms.

    Science.gov (United States)

    Brockhurst, Michael A; Hochberg, Michael E; Bell, Thomas; Buckling, Angus

    2006-10-24

    Resource competition within a group of cooperators is expected to decrease selection for cooperative behavior but can also result in diversifying selection for the use of different resources, which in turn could retard the breakdown of cooperation. Diverse groups are likely to be less susceptible to invasion by noncooperating social cheats: First, competition repression resulting from character displacement may provide less of a selective advantage to cheating; second, cheats may trade off the ability to exploit cooperators that specialize in one type of resource against cooperators that specialize in another ; third, diverse communities of any kind may have higher invasion resistance because there are fewer resources available for an invader to use . Furthermore, diverse groups are likely to be more productive than clonal groups if a wider range of total resources are being used . We addressed these issues by using the cooperative trait of biofilm formation in Pseudomonas fluorescens. Character displacement through resource competition evolved within biofilms; productivity increased with increasing character displacement, and diverse biofilms were less susceptible to invasion by cheats. These results demonstrate that diversification into different ecological niches can minimize selection against cooperation in the face of local resource competition.

  17. Social image concerns promote cooperation more than altruistic punishment

    Science.gov (United States)

    Grimalda, Gianluca; Pondorfer, Andreas; Tracer, David P.

    2016-01-01

    Human cooperation is enigmatic, as organisms are expected, by evolutionary and economic theory, to act principally in their own interests. However, cooperation requires individuals to sacrifice resources for each other's benefit. We conducted a series of novel experiments in a foraging society where social institutions make the study of social image and punishment particularly salient. Participants played simple cooperation games where they could punish non-cooperators, promote a positive social image or do so in combination with one another. We show that although all these mechanisms raise cooperation above baseline levels, only when social image alone is at stake do average economic gains rise significantly above baseline. Punishment, either alone or combined with social image building, yields lower gains. Individuals' desire to establish a positive social image thus emerges as a more decisive factor than punishment in promoting human cooperation. PMID:27504898

  18. Asymmetric evaluation promotes cooperation in network population

    Science.gov (United States)

    Shen, Chen; Li, Xiaoping; Shi, Lei; Deng, Zhenghong

    2017-05-01

    The evolution of cooperation remains a fundamental challenge in human society. Many previous studies investigated these questions via spatial reciprocity, where players obtain their payoffs by interacting with their direct neighbors. It has also been verified that environmental factors can influence the evolution of cooperation theoretically and empirically. In reality, however, individuals may have the limit knowledge about their indirect neighbors. Inspired by this fact, we consider an asymmetric fitness calculation mechanism, which only integrates the environment factors into the focal player, to explore the evolution of cooperation. Here, the environmental factor is defined as the average payoff of all individual neighbors, which is regulated by a tunable parameter u. Through numerical simulation, we find that, compared with the traditional version (u = 0), that the cooperation level can be greatly enhanced when u is positive. Interestingly, the larger the value of u, the higher the level of cooperation. Finally, to explore the generality of this finding, we have tested the results on different topologies.

  19. Robotic Cooperative Learning Promotes Student STEM Interest

    Science.gov (United States)

    Mosley, Pauline; Ardito, Gerald; Scollins, Lauren

    2016-01-01

    The principal purpose of this investigation is to study the effect of robotic cooperative learning methodologies on middle school students' critical thinking, and STEM interest. The semi-experimental inquiry consisted of ninety four six-grade students (forty nine students in the experimental group, forty five students in the control group), chosen…

  20. Adaptive long-range migration promotes cooperation under tempting conditions.

    Science.gov (United States)

    Ichinose, Genki; Saito, Masaya; Sayama, Hiroki; Wilson, David Sloan

    2013-01-01

    Migration is a fundamental trait in humans and animals. Recent studies investigated the effect of migration on the evolution of cooperation, showing that contingent migration favors cooperation in spatial structures. In those studies, only local migration to immediate neighbors was considered, while long-range migration has not been considered yet, partly because the long-range migration has been generally regarded as harmful for cooperation as it would bring the population to a well-mixed state that favors defection. Here, we studied the effects of adaptive long-range migration on the evolution of cooperation through agent-based simulations of a spatial Prisoner's Dilemma game where individuals can jump to a farther site if they are surrounded by more defectors. Our results show that adaptive long-range migration strongly promotes cooperation, especially under conditions where the temptation to defect is considerably high. These findings demonstrate the significance of adaptive long-range migration for the evolution of cooperation.

  1. 78 FR 53481 - U.S.-Canada Regulatory Cooperation Council Stakeholder Request for Comment Summer 2013

    Science.gov (United States)

    2013-08-29

    ... From the Federal Register Online via the Government Publishing Office ] OFFICE OF MANAGEMENT AND...: Executive Office of the President, Office of Management and Budget. ACTION: Notice. In recognition of the... point and clear motivation for deepening regulatory cooperation. Regulatory cooperation is not about...

  2. Social role specialization promotes cooperation between parents.

    Science.gov (United States)

    Barta, Zoltán; Székely, Tamás; Liker, András; Harrison, Freya

    2014-06-01

    Biparental care of offspring is a widespread social behavior, and various ecological, life-history, and demographic factors have been proposed to explain its evolution and maintenance. Raising offspring generally requires several types of care (e.g., feeding, brooding, and defense), and males and females often specialize in providing different types of care. However, theoretical models of care often assume that care is a single variable and hence that a unit of care by the mother is interchangeable with a unit of care by the father. We hypothesize that the ability of one parent to provide all types of care may be limited by nonadditive costs or by sex-based asymmetries in the costs of particular care types. Using an individual-based simulation, we show that synergistic costs of investing in two tasks or negligible sex-based cost asymmetries select for task specialization and biparental care. Biparental care persists despite intense sexual selection and sex-biased mortality, suggesting that previous models make overly restrictive predictions of the conditions under which cooperation can be maintained. Our model provides a mechanistic underpinning for published models that show that the synergistic benefits of individuals cooperating can stabilize cooperation, both in the context of parental care and in other social scenarios.

  3. Centralized sanctioning and legitimate authority promote cooperation in humans.

    Science.gov (United States)

    Baldassarri, Delia; Grossman, Guy

    2011-07-05

    Social sanctioning is widely considered a successful strategy to promote cooperation among humans. In situations in which individual and collective interests are at odds, incentives to free-ride induce individuals to refrain from contributing to public goods provision. Experimental evidence from public goods games shows that when endowed with sanctioning powers, conditional cooperators can discipline defectors, thus leading to greater levels of cooperation. However, extant evidence is based on peer punishment institutions, whereas in complex societies, systems of control are often centralized: for instance, we do not sanction our neighbors for driving too fast, the police do. Here we show the effect of centralized sanctioning and legitimate authority on cooperation. We designed an adaptation of the public goods game in which sanctioning power is given to a single monitor, and we experimentally manipulated the process by which the monitor is chosen. To increase the external validity of the study, we conducted lab-in-the-field experiments involving 1,543 Ugandan farmers from 50 producer cooperatives. This research provides evidence of the effectiveness of centralized sanctioning and demonstrates the causal effect of legitimacy on cooperation: participants are more responsive to the authority of an elected monitor than a randomly chosen monitor. Our essay contributes to the literature on the evolution of cooperation by introducing the idea of role differentiation. In complex societies, cooperative behavior is not only sustained by mechanisms of selection and reciprocity among peers, but also by the legitimacy that certain actors derive from their position in the social hierarchy.

  4. Promoting entrepreneurship through University-Industry cooperation

    OpenAIRE

    Cardoso, Eduardo Luís; Carvalho, Marta

    2015-01-01

    Entrepreneurship has been considered, by different academics and policy makers, as a mean to foster economic development and job creation, but also as an ability to promote a more dynamic, creative, innovative, competitive and sustainable society. Overcoming difficulties in the development of academic entrepreneurship are included in the required objectives of bridging the gap between research and innovation in Europe and, thus, is a challenge for universities. The prevailing f...

  5. Uncovering cis regulatory codes using synthetic promoter shuffling.

    Directory of Open Access Journals (Sweden)

    Ali Kinkhabwala

    Full Text Available Revealing the spectrum of combinatorial regulation of transcription at individual promoters is essential for understanding the complex structure of biological networks. However, the computations represented by the integration of various molecular signals at complex promoters are difficult to decipher in the absence of simple cis regulatory codes. Here we synthetically shuffle the regulatory architecture--operator sequences binding activators and repressors--of a canonical bacterial promoter. The resulting library of complex promoters allows for rapid exploration of promoter encoded logic regulation. Among all possible logic functions, NOR and ANDN promoter encoded logics predominate. A simple transcriptional cis regulatory code determines both logics, establishing a straightforward map between promoter structure and logic phenotype. The regulatory code is determined solely by the type of transcriptional regulation combinations: two repressors generate a NOR: NOT (a OR b whereas a repressor and an activator generate an ANDN: a AND NOT b. Three-input versions of both logics, having an additional repressor as an input, are also present in the library. The resulting complex promoters cover a wide dynamic range of transcriptional strengths. Synthetic promoter shuffling represents a fast and efficient method for exploring the spectrum of complex regulatory functions that can be encoded by complex promoters. From an engineering point of view, synthetic promoter shuffling enables the experimental testing of the functional properties of complex promoters that cannot necessarily be inferred ab initio from the known properties of the individual genetic components. Synthetic promoter shuffling may provide a useful experimental tool for studying naturally occurring promoter shuffling.

  6. Reputation-based partner choice promotes cooperation in social networks.

    Science.gov (United States)

    Fu, Feng; Hauert, Christoph; Nowak, Martin A; Wang, Long

    2008-08-01

    We investigate the cooperation dynamics attributed to the interplay between the evolution of individual strategies and evolution of individual partnerships. We focus on the effect of reputation on an individual's partner-switching process. We assume that individuals can either change their strategies by imitating their partners or adjust their partnerships based on local information about reputations. We manipulate the partner switching in two ways; that is, individuals can switch from the lowest reputation partners, either to their partners' partners who have the highest reputation (i.e., ordering in partnership) or to others randomly chosen from the entire population (i.e., randomness in partnership). We show that when individuals are able to alter their behavioral strategies and their social interaction partnerships on the basis of reputation, cooperation can prevail. We find that the larger temptation to defect and the denser the partner network, the more frequently individuals need to shift their partnerships in order for cooperation to thrive. Furthermore, an increasing tendency of switching to partners' partners is more likely to lead to a higher level of cooperation. We show that when reputation is absent in such partner-switching processes, cooperation is much less favored than that of the reputation involved. Moreover, we investigate the effect of discounting an individual's reputation on the evolution of cooperation. Our results highlight the importance of the consideration of reputation (indirect reciprocity) on the promotion of cooperation when individuals can adjust their partnerships.

  7. Promotion of technical cooperation in the field of energy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jung Kyung; Jung, Duk Yung; Suh, Seong Seog; Park, Myung Nam; Kim, Young Mi; Cho, Moo Kyung [Korea Inst. of Energy Research, Taejon (Korea, Republic of)

    1995-12-01

    This study aims to improve the quality of human resources and the capability of research and development through the promotion of technical cooperation with foreign energy organizations possessing advanced technologies, and at the same time to contribute to internationalizing energy technology through the active involvement in multilateral technical cooperation programs with international organizations. To attain these aims, practical cooperative relations has been strengthened with 34 organizations from 11 countries including 6 organizations with which new cooperative agreements has been concluded in 1995 from the USA, Australia, China, and Russia, through the promotion of the continuous exchange of information and personnel, and international joint projects. And also the positive participation in technical cooperation programs and research projects organized or sponsored by APEC, IEA, UNDP, UNESCO, WEC has been made. In addition, for the improvement in research capability, 200 researchers has been dispatched abroad for the presentation of papers, of for the discussion of joint research projects, and 30 foreign experts through diverse overseas personnel exchange programs including Brain Pool Program were invited for the contribution of advancing research projects. (author). 8 figs., 15 tabs.

  8. Learning Microbiology Through Cooperation: Designing Cooperative Learning Activities that Promote Interdependence, Interaction, and Accountability.

    Science.gov (United States)

    Trempy, Janine E; Skinner, Monica M; Siebold, William A

    2002-05-01

    A microbiology course and its corresponding learning activities have been structured according to the Cooperative Learning Model. This course, The World According to Microbes, integrates science, math, engineering, and technology (SMET) majors and non-SMET majors into teams of students charged with problem solving activities that are microbial in origin. In this study we describe development of learning activities that utilize key components of Cooperative Learning-positive interdependence, promotive interaction, individual accountability, teamwork skills, and group processing. Assessments and evaluations over an 8-year period demonstrate high retention of key concepts in microbiology and high student satisfaction with the course.

  9. Learning Microbiology Through Cooperation: Designing Cooperative Learning Activities that Promote Interdependence, Interaction, and Accountability

    Directory of Open Access Journals (Sweden)

    Janine E. Trempy

    2009-12-01

    Full Text Available A microbiology course and its corresponding learning activities have been structured according to the Cooperative Learning Model. This course, The World According to Microbes, integrates science, math, engineering, and technology (SMET majors and non-SMET majors into teams of students charged with problem solving activities that are microbial in origin. In this study we describe development of learning activities that utilize key components of Cooperative Learning—positive interdependence, promotive interaction, individual accountability, teamwork skills, and group processing. Assessments and evaluations over an 8-year period demonstrate high retention of key concepts in microbiology and high student satisfaction with the course.

  10. Social influence promotes cooperation in the public goods game

    Science.gov (United States)

    Wu, Te; Fu, Feng; Dou, Puxuan; Wang, Long

    2014-11-01

    Previous studies mainly consider the random selection pattern in which individuals randomly choose reference models from their neighbors for strategy updating. However, the random selection pattern is unable to capture all real world circumstances. We institute a spatial model to investigate the effects of influence-based reference selection pattern on the evolution of cooperation in the context of public goods games. Whenever experiencing strategy updating, all the individuals each choose one of its neighbors as a reference with the probability proportional to this neighbor’s influence. Levels of individuals’ influence are dynamical. When an individual is imitated, the level of its influence increases, thus constituting a positive feedback between the frequencies of individuals being imitated and the likelihood for them to be reference models. We find that the level of collective cooperation can be enhanced whenever the influence-based reference selection pattern is integrated into the strategy updating process. Results also show that the evolution of cooperation can be promoted when the increase in individuals’ frequency of being imitated upholds their influence in large magnitude. Our work may improve the understanding of how influence-based selection patterns promote cooperative behavior.

  11. Multiple Interferon Regulatory Factor and NF-κB Sites Cooperate in Mediating Cell-Type- and Maturation-Specific Activation of the Human CD83 Promoter in Dendritic Cells

    OpenAIRE

    Stein, Marcello F.; Lang, Stefan; Winkler, Thomas H.; Deinzer, Andrea; Erber, Sebastian; Nettelbeck, Dirk M.; Naschberger, Elisabeth; Jochmann, Ramona; Stürzl, Michael; Slany, Robert K.; Werner, Thomas; Steinkasserer, Alexander; Knippertz, Ilka

    2013-01-01

    CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms regulating this DC- and maturation-specific CD83 expression, chromatin immunoprecipitation (ChIP)-on-chip microarray, biocomputational, reporter, electrophoretic mobility shift assay (EMSA), and ChIP analyses were performed. These studies led ...

  12. Promotion of cooperation in evolutionary game dynamics with local information.

    Science.gov (United States)

    Liu, Xuesong; Pan, Qiuhui; He, Mingfeng

    2018-01-21

    In this paper, we propose a strategy-updating rule driven by local information, which is called Local process. Unlike the standard Moran process, the Local process does not require global information about the strategic environment. By analyzing the dynamical behavior of the system, we explore how the local information influences the fixation of cooperation in two-player evolutionary games. Under weak selection, the decreasing local information leads to an increase of the fixation probability when natural selection does not favor cooperation replacing defection. In the limit of sufficiently large selection, the analytical results indicate that the fixation probability increases with the decrease of the local information, irrespective of the evolutionary games. Furthermore, for the dominance of defection games under weak selection and for coexistence games, the decreasing of local information will lead to a speedup of a single cooperator taking over the population. Overall, to some extent, the local information is conducive to promoting the cooperation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Promoting Corporate Social Responsibility in Logistics throughout Horizontal Cooperation

    Directory of Open Access Journals (Sweden)

    Angel A. Juan

    2014-03-01

    Full Text Available This paper discusses how Corporate Social Responsibility (CSR can be promoted in Logistics and Transportation (L&T companies by means of Horizontal Cooperation (HC practices. The L&T sector is experiencing important changes because of new trends in markets and society. These changes have a strong impact on the way L&T companies develop their distribution activities.On the one hand, globalisation and increasing competition are creating incentives for these companies to cooperate in different ways – with the aim of becoming more efficient by sharing resources and reducing costs. On the other hand, the increasing sustainability awareness within society is pressuring L&T companies to integrate CSR principles into their strategies and policies. Accordingly, this paper discusses the current trends in these areas and offers some examples of how HC can contribute to reduce both distributions costs as well as the environmental impact of the distribution activities.

  14. 76 FR 18165 - Request for Public Comments Concerning Regulatory Cooperation Activities That Would Help...

    Science.gov (United States)

    2011-04-01

    ... activities between or among the United States, Mexico, and Canada: Information-sharing agreements; technical... will serve as a basis for bilateral and trilateral discussion with Canada and Mexico on regulatory cooperation activities to undertake which will support the President's National Export Initiative and serve as...

  15. 77 FR 17569 - United States-Canada Regulatory Cooperation Council (RCC)-Transportation-Dangerous Goods Working...

    Science.gov (United States)

    2012-03-26

    ... (RCC)-- Transportation--Dangerous Goods Working Group AGENCY: Pipeline and Hazardous Materials Safety... Transportation--Dangerous Goods Working Group, of the United States-Canada Regulatory Cooperation Council (RCC... address the dangerous goods (hazardous materials) transportation opportunities identified in the Joint...

  16. Promotion of Bilateral Cooperative Programs in Nuclear Human Resources Development

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E. J.; Han, K. W.; Nam, Y. M. (and others)

    2009-08-15

    The purpose of this project is strengthening of bilateral cooperation with those countries for sharing Korea's technology, and providing of education and training on Korean experience regarding national nuclear policy, technology self reliance, and technology itself, in the field of nuclear power generation and the application of radioisotopes and radiation. This project covers an analysis on the need of nuclear human resource development in countries having interest in the introduction of nuclear power and/or promotion of the use of nuclear energy, and provision of courses on 'nuclear power policy, planning and management' and 'design and operation of nuclear research reactor, and application of radiation technology' along with the country specific needs. Education and training of key members in nuclear energy development from Egypt: It was implemented through bilateral cooperation and support by KOICA program. The first part, which targeted staff members from Egypt Nuclear Commission, was held for 2 months providing a KOICA course on policy, planning and management for nuclear power project, and second part was on the job training in Korea Hydro and Nuclear Power and Korea Institute of Nuclear Safety, KAERI respectively. On the job training of 1 scientist from Vietnam was implemented on the basis of bilateral cooperation in a research laboratory on radioactive waste treatment technology, at KAERI. Education and training for scientists from South East RCA countries were carried out for 11 participants from Vietnam, Thailand, Indonesia, China, Pakistan, Malaysia, Philippines, and Bangladesh. The course dealt with nuclear research reactor and radiation application technology. Development of nuclear education and training programs for key persons involved in nuclear power projects from countries of Middle East: The developed program consists of 15 courses addressing 3 technical levels, i.e. high level policy makers, middle level project

  17. The increased risk of joint venture promotes social cooperation.

    Directory of Open Access Journals (Sweden)

    Te Wu

    Full Text Available The joint venture of many members is common both in animal world and human society. In these public enterprizes, highly cooperative groups are more likely to while low cooperative groups are still possible but not probable to succeed. Existent literature mostly focuses on the traditional public goods game, in which cooperators create public wealth unconditionally and benefit all group members unbiasedly. We here institute a model addressing this public goods dilemma with incorporating the public resource foraging failure risk. Risk-averse individuals tend to lead a autarkic life, while risk-preferential ones tend to participate in the risky public goods game. For participants, group's success relies on its cooperativeness, with increasing contribution leading to increasing success likelihood. We introduce a function with one tunable parameter to describe the risk removal pattern and study in detail three representative classes. Analytical results show that the widely replicated population dynamics of cyclical dominance of loner, cooperator and defector disappear, while most of the time loners act as savors while eventually they also disappear. Depending on the way that group's success relies on its cooperativeness, either cooperators pervade the entire population or they coexist with defectors. Even in the later case, cooperators still hold salient superiority in number as some defectors also survive by parasitizing. The harder the joint venture succeeds, the higher level of cooperation once cooperators can win the evolutionary race. Our work may enrich the literature concerning the risky public goods games.

  18. The increased risk of joint venture promotes social cooperation.

    Science.gov (United States)

    Wu, Te; Fu, Feng; Zhang, Yanling; Wang, Long

    2013-01-01

    The joint venture of many members is common both in animal world and human society. In these public enterprizes, highly cooperative groups are more likely to while low cooperative groups are still possible but not probable to succeed. Existent literature mostly focuses on the traditional public goods game, in which cooperators create public wealth unconditionally and benefit all group members unbiasedly. We here institute a model addressing this public goods dilemma with incorporating the public resource foraging failure risk. Risk-averse individuals tend to lead a autarkic life, while risk-preferential ones tend to participate in the risky public goods game. For participants, group's success relies on its cooperativeness, with increasing contribution leading to increasing success likelihood. We introduce a function with one tunable parameter to describe the risk removal pattern and study in detail three representative classes. Analytical results show that the widely replicated population dynamics of cyclical dominance of loner, cooperator and defector disappear, while most of the time loners act as savors while eventually they also disappear. Depending on the way that group's success relies on its cooperativeness, either cooperators pervade the entire population or they coexist with defectors. Even in the later case, cooperators still hold salient superiority in number as some defectors also survive by parasitizing. The harder the joint venture succeeds, the higher level of cooperation once cooperators can win the evolutionary race. Our work may enrich the literature concerning the risky public goods games.

  19. Cooperation of public administration and third sector in sport promotion in Prague 11

    OpenAIRE

    Soucha, Matěj

    2014-01-01

    Title: Cooperation of public administration and third sector in sport promotion in Prague 11 Objectives: To describe and to assess the status of providing promotion of sport in Prague 11 Methods: Mixed research, case study, personal interview, questionnaire Results: The status of providing promotion of sport in Prague 11 was described. Based on the ascertainment of local sport organizations representative's opinions on sport environment in Prague 11 current problems in cooperation of public a...

  20. Harnessing the Power of Reputation: Strengths and Limits for Promoting Cooperative Behaviors

    Directory of Open Access Journals (Sweden)

    Pat Barclay

    2012-12-01

    Full Text Available Evolutionary approaches have done much to identify the pressures that select for cooperative sentiment. This helps us understand when and why cooperation will arise, and applied research shows how these pressures can be harnessed to promote various types of cooperation. In particular, recent evidence shows how opportunities to acquire a good reputation can promote cooperation in laboratory and applied settings. Cooperation can be promoted by tapping into forces like indirect reciprocity, costly signaling, and competitive altruism. When individuals help others, they receive reputational benefits (or avoid reputational costs, and this gives people an incentive to help. Such findings can be applied to promote many kinds of helping and cooperation, including charitable donations, tax compliance, sustainable and pro-environmental behaviors, risky heroism, and more. Despite the potential advantages of using reputation to promote positive behaviors, there are several risks and limits. Under some circumstances, opportunities for reputation will be ineffective or promote harmful behaviors. By better understanding the dynamics of reputation and the circumstances under which cooperation can evolve, we can better design social systems to increase the rate of cooperation and reduce conflict.

  1. Loregic: a method to characterize the cooperative logic of regulatory factors.

    Directory of Open Access Journals (Sweden)

    Daifeng Wang

    2015-04-01

    Full Text Available The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible two-input-one-output logic gates (e.g. AND or XOR to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet's observed gene expression pattern across many conditions. We make Loregic available as a general-purpose tool (github.com/gersteinlab/loregic. We validate it with known yeast transcription-factor knockout experiments. Next, using human ENCODE ChIP-Seq and TCGA RNA-Seq data, we are able to demonstrate how Loregic characterizes complex circuits involving both proximally and distally regulating transcription factors (TFs and also miRNAs. Furthermore, we show that MYC, a well-known oncogenic driving TF, can be modeled as acting independently from other TFs (e.g., using OR gates but antagonistically with repressing miRNAs. Finally, we inter-relate Loregic's gate logic with other aspects of regulation, such as indirect binding via protein-protein interactions, feed-forward loop motifs and global regulatory hierarchy.

  2. Distinguishing the opponents promotes cooperation in well-mixed populations

    Science.gov (United States)

    Wardil, Lucas; da Silva, Jafferson K. L.

    2010-03-01

    Cooperation has been widely studied when an individual strategy is adopted against all coplayers. In this context, some extra mechanisms, such as punishment, reward, memory, and network reciprocity must be introduced in order to keep cooperators alive. Here, we adopt a different point of view. We study the adoption of different strategies against different opponents instead of adoption of the same strategy against all of them. In the context of the prisoner dilemma, we consider an evolutionary process in which strategies that provide more benefits are imitated and the players replace the strategy used in one of the interactions furnishing the worst payoff. Individuals are set in a well-mixed population, so that network reciprocity effect is excluded and both synchronous and asynchronous updates are analyzed. As a consequence of the replacement rule, we show that mutual cooperation is never destroyed and the initial fraction of mutual cooperation is a lower bound for the level of cooperation. We show by simulation and mean-field analysis that (i) cooperation dominates for synchronous update and (ii) only the initial mutual cooperation is maintained for asynchronous update. As a side effect of the replacement rule, an “implicit punishment” mechanism comes up in a way that exploitations are always neutralized providing evolutionary stability for cooperation.

  3. Heterogeneous game resource distributions promote cooperation in spatial prisoner's dilemma game

    Science.gov (United States)

    Cui, Guang-Hai; Wang, Zhen; Yang, Yan-Cun; Tian, Sheng-Wen; Yue, Jun

    2018-01-01

    In social networks, individual abilities to establish interactions are always heterogeneous and independent of the number of topological neighbors. We here study the influence of heterogeneous distributions of abilities on the evolution of individual cooperation in the spatial prisoner's dilemma game. First, we introduced a prisoner's dilemma game, taking into account individual heterogeneous abilities to establish games, which are determined by the owned game resources. Second, we studied three types of game resource distributions that follow the power-law property. Simulation results show that the heterogeneous distribution of individual game resources can promote cooperation effectively, and the heterogeneous level of resource distributions has a positive influence on the maintenance of cooperation. Extensive analysis shows that cooperators with large resource capacities can foster cooperator clusters around themselves. Furthermore, when the temptation to defect is high, cooperator clusters in which the central pure cooperators have larger game resource capacities are more stable than other cooperator clusters.

  4. Contribution diversity and incremental learning promote cooperation in public goods games

    Science.gov (United States)

    Liu, Penghui; Liu, Jing

    2017-11-01

    Understanding the evolution of cooperation in nature has long been a challenge and how to promote cooperation in public goods games (PGG) has attracted lots of attention recently. Social diversity has been found helpful to explain the emergence of cooperation in the absence of reputation and punishment. However, further refinement on how individuals reallocate their contribution to each PGG remains an open question. Moreover, individuals in existing works mostly teach or learn from neighbors according to their payoff in the last generation only. However, individuals in reality are preferred to learn from others with a long-term good performance. Therefore, in this paper, a new contribution diversity (CD) is designed and incremental learning (IL) is introduced. We investigate how these two may influence the evolution of cooperation in PGG. Based on the simulation results, we found that both the CD and IL can promote the cooperation in PGGs. Moreover, when cooperators are shaken in their strategy, CD may fail in reallocating contribution of individuals properly. However, IL is found effective to stabilize faith of cooperators and cooperators under IL reflect a long-term advantage over defectors in terms of benefits. Therefore, we further find IL and CD can mutually benefit each other in promoting cooperation, as CD can reasonably adjust the investment of cooperators while IL can provide more information to CD.

  5. Friendship-based partner switching promotes cooperation in heterogeneous populations

    Science.gov (United States)

    Chen, Wei; Wu, Te; Li, Zhiwu; Wang, Long

    2016-02-01

    The forming of human social ties tends to be with similar individuals. This study concentrates on the emergence of cooperation among heterogeneous populations. A simple model is proposed by considering the impact of interplay between the evolution of strategies and that of social partnerships on cooperation dynamics. Whenever two individuals acquire the rewards by playing prisoner's dilemma game with each other, the friendship (friendship is quantified as the weight of a link) between the two individuals deepens. Individuals can switch off the social ties with the partners who are unfriendly and rewire to similar new ones. Under this partner switching mechanism, population structure is divided into several groups and cooperation can prevail. It is observed that the frequent tendency of partner switching can lead to the enhancement of cooperative behavior under the enormous temptation to defect. Moreover, the influence of discounting the relationship between different individuals is also investigated. Meanwhile, the cooperation prevails when the adjustment of friendships mainly depends on the incomes of selected individuals rather than that of their partners. Finally, it is found that too similar population fail to maximize the cooperation and there exists a moderate similarity that can optimize cooperation.

  6. Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

    Science.gov (United States)

    Casati, S; Aschberger, K; Barroso, J; Casey, W; Delgado, I; Kim, T S; Kleinstreuer, N; Kojima, H; Lee, J K; Lowit, A; Park, H K; Régimbald-Krnel, M J; Strickland, J; Whelan, M; Yang, Y; Zuang, Valérie

    2018-02-01

    Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate

  7. When prevention promotes creativity: the role of mood, regulatory focus, and regulatory closure.

    Science.gov (United States)

    Baas, Matthijs; De Dreu, Carsten K W; Nijstad, Bernard A

    2011-05-01

    Promotion-focused states generally boost creativity because they associate with enhanced activation and cognitive flexibility. With regard to prevention-focused states, research evidence is less consistent, with some findings suggesting prevention-focused states promote creativity and other findings pointing to no or even negative effects. We proposed and tested the hypothesis that whether prevention-focused states boost creativity depends on regulatory closure (whether a goal is fulfilled or not). We predicted that prevention-focused states that activate the individual (unfulfilled prevention goals, fear) would lead to similar levels of creativity as promotion-focused states but that prevention-focused states that deactivate (closed prevention goals, relief) would lead to lower levels of creativity. Moreover, we predicted that this effect would be mediated by feelings of activation. Predictions were tested in 3 studies on creative insights and 1 on original ideation. Results supported predictions. Implications for self-regulation, motivation, mood, and creativity are discussed. (c) 2011 APA, all rights reserved.

  8. Order without law: Reputation promotes cooperation in a cryptomarket for illegal drugs

    NARCIS (Netherlands)

    Przepiorka, W.|info:eu-repo/dai/nl/413317617; Norbutas, L.|info:eu-repo/dai/nl/413306755; Corten, R.|info:eu-repo/dai/nl/304835145

    2017-01-01

    The emergence of large-scale cooperation in humans poses a major puzzle for the social and behavioural sciences. Reputation formation—individuals’ ability to share information about others’ deeds and misdeeds—has been found to promote cooperation. However, these findings are mostly based on

  9. Harnessing the Power of Reputation: Strengths and Limits for Promoting Cooperative Behaviors

    National Research Council Canada - National Science Library

    Barclay, Pat

    2012-01-01

    ...), and this gives people an incentive to help. Such findings can be applied to promote many kinds of helping and cooperation, including charitable donations, tax compliance, sustainable and pro-environmental behaviors, risky heroism, and more...

  10. CooperativesPromoters of Social Economy in Romania

    Directory of Open Access Journals (Sweden)

    Martin Balogh,

    2012-12-01

    Full Text Available The present article makes an analysis of cooperatives in Romania in terms of their role in the context of socio-economic development of society by generating new jobs and social integration, by eradicating poverty and by inclusion of vulnerable groups and categories. Since the cooperative phenomenon has become a highly visible and present one in the European and Romanian public life, through this paper we want to answer a series of questions related to the occurrence and evolution of cooperatives at national and international level, the approaches to this phenomenon which have emerged at European level and which are the regulations governing their organization and operation in the Romanian space.

  11. Promoting Cooperative Learning in the Classroom: Comparing Explicit and Implicit Training Techniques

    Directory of Open Access Journals (Sweden)

    Anne Elliott

    2003-07-01

    Full Text Available In this study, we investigated whether providing 4th and 5th-grade students with explicit instruction in prerequisite cooperative-learning skills and techniques would enhance their academic performance and promote in them positive attitudes towards cooperative learning. Overall, students who received explicit training outperformed their peers on both the unit project and test and presented more favourable attitudes towards cooperative learning. The findings of this study support the use of explicitly instructing students about the components of cooperative learning prior to engaging in collaborative activities. Implications for teacher-education are discussed.

  12. Promoting cooperation by preventing exploitation: The role of network structure

    Science.gov (United States)

    Utkovski, Zoran; Stojkoski, Viktor; Basnarkov, Lasko; Kocarev, Ljupco

    2017-08-01

    A growing body of empirical evidence indicates that social and cooperative behavior can be affected by cognitive and neurological factors, suggesting the existence of state-based decision-making mechanisms that may have emerged by evolution. Motivated by these observations, we propose a simple mechanism of anonymous network interactions identified as a form of generalized reciprocity—a concept organized around the premise "help anyone if helped by someone'—and study its dynamics on random graphs. In the presence of such a mechanism, the evolution of cooperation is related to the dynamics of the levels of investments (i.e., probabilities of cooperation) of the individual nodes engaging in interactions. We demonstrate that the propensity for cooperation is determined by a network centrality measure here referred to as neighborhood importance index and discuss relevant implications to natural and artificial systems. To address the robustness of the state-based strategies to an invasion of defectors, we additionally provide an analysis which redefines the results for the case when a fraction of the nodes behave as unconditional defectors.

  13. Cooperation, trust, and antagonism: How public goods are promoted

    NARCIS (Netherlands)

    Parks, C.D.; Joireman, J.; van Lange, P.A.M.

    2013-01-01

    One of the most continually vexing problems in society is the variability with which citizens support endeavors that are designed to help a great number of people. In this article, we examine the twin roles of cooperative and antagonistic behavior in this variability. We find that each plays an

  14. Promotion of cooperation induced by two-sided players in prisoner's dilemma game

    Science.gov (United States)

    Su, Zhen; Li, Lixiang; Xiao, Jinghua; Podobnik, B.; Stanley, H. Eugene

    2018-01-01

    We examine how real-world individuals and companies can either reach an agreement or fail to reach an agreement after several stages of negotiation. We use a modified prisoner's dilemma game with two-sided players who can either cooperate or not cooperate with their neighbors. We find that the presence of even a small number of these two-sided players substantially promotes the cooperation because, unlike the rock-paper-scissors scenario, when the cooperators change to the non-cooperators to gain a payoff, they can turn to the two-sided players and continue negotiating. We find that the network structure influences the spread of strategies. Lattice and regular-random (RR) networks benefit the spread of both non-cooperation and two-sided strategies, but scale-free (SF) networks stop both strategies. We also find that the Erdös-R e ´ nyi (ER) network promotes the two-sided strategy and blocks the spread of non-cooperation. As the ER network density decreases, and the network degree is lowered the lifetime of non-cooperators increases. Our results expand our understanding of the role played by the two-sided strategy in the growth of the cooperative behavior in networks.

  15. Online Cooperative Promotion and Cost Sharing Policy under Supply Chain Competition

    Directory of Open Access Journals (Sweden)

    Erjiang E

    2016-01-01

    Full Text Available This paper studies online cooperative promotion and cost sharing decisions in competing supply chains. We consider a model of one B2C e-commerce platform and two supply chains each consisting of a supplier and an online retailer. The problem is studied using a multistage game. Firstly, the e-commerce platform carries out the cooperative promotion and sets the magnitude of markdown (the value of e-coupon. Secondly, each retailer and his supplier determine the fraction of promotional cost sharing when they have different bargaining power. Lastly, the retailers decide whether to participate in the cooperative promotion campaign. We show that the retailers are likely to participate in the promotion if consumers become more price-sensitive. However, it does not imply that the retailers can benefit from the price promotion; the promotion decision game resembles the classical prisoner’s dilemma game. The retailers and suppliers can benefit from the cooperative promotion by designing an appropriate cost sharing contract. For a supply chain, the bargaining power between supplier and retailer, consumer price sensitivity, and competition intensity affect the fraction of the promotional cost sharing. We also find that equilibrium value of e-coupon set by the e-commerce platform is not optimal for all the parties.

  16. Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice

    Science.gov (United States)

    García-Ramírez, Idoia; Tadros, Saber; González-Herrero, Inés; Martín-Lorenzo, Alberto; Rodríguez-Hernández, Guillermo; Moore, Dalia; Ruiz-Roca, Lucía; Blanco, Oscar; Alonso-López, Diego; Rivas, Javier De Las; Hartert, Keenan; Duval, Romain; Klinkebiel, David; Bast, Martin; Vose, Julie; Lunning, Matthew; Fu, Kai; Greiner, Timothy; Rodrigues-Lima, Fernando; Jiménez, Rafael; Criado, Francisco Javier García; Cenador, María Begoña García; Brindle, Paul; Vicente-Dueñas, Carolina; Alizadeh, Ash; Sánchez-García, Isidro

    2017-01-01

    CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 overexpression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B cells, we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these 2 diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared with FL. Together, our data therefore provide important links between Crebbp inactivation and Bcl2 dependence and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein. PMID:28288979

  17. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis

    Science.gov (United States)

    Wang, L; Ray, A; Jiang, X; Wang, J-y; Basu, S; Liu, X; Qian, T; He, R; Dittel, B N; Chu, Y

    2015-01-01

    Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10−/− B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis. PMID:25807185

  18. Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors.

    Science.gov (United States)

    Zabidi, Muhammad A; Stark, Alexander

    2016-12-01

    Gene expression is regulated by genomic enhancers that recruit transcription factors and cofactors to activate transcription from target core promoters. Over the past years, thousands of enhancers and core promoters in animal genomes have been annotated, and we have learned much about the domain structure in which regulatory genomes are organized in animals. Enhancer-core-promoter targeting occurs at several levels, including regulatory domains, DNA accessibility, and sequence-encoded core-promoter specificities that are likely mediated by different regulatory proteins. We review here current knowledge about enhancer-core-promoter targeting, regulatory communication between enhancers and core promoters, and the protein factors involved. We conclude with an outlook on open questions that we find particularly interesting and that will likely lead to additional insights in the upcoming years. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Diversity of neighborhoods promotes cooperation in evolutionary social dilemmas

    Science.gov (United States)

    Ma, Yongjuan; Lu, Jun; Shi, Lei

    2017-02-01

    Explaining the evolution of cooperative behavior is one of the most important and interesting problems in a myriad of disciplines, such as evolutionary biology, mathematics, statistical physics, social science and economics Up to now, there have been a great number of works aiming to this issue with the help of evolutionary game theory. However, vast majority of existing literatures simply assume that the interaction neighborhood and replacement neighborhood are symmetric, which seems inconsistent with real-world cases. In this paper, we consider the asymmetrical neighborhood: player of type A, whose factor is controlled by a parameter τ, has four interaction neighbors and four replacement neighbors, while player of type B, whose factor is controlled by a parameter 1 - τ, possess eight interaction neighbors and four replacement neighbors. By means of numerous Monte Carlo simulations, we found that middle τ can make the cooperation reach the highest level While for this finding, its robustness can be further validated in more games.

  20. Promoting Arab and Israeli cooperation: peacebuilding through health initiatives.

    Science.gov (United States)

    Skinner, Harvey; Abdeen, Ziad; Abdeen, Hani; Aber, Phil; Al-Masri, Mohammad; Attias, Joseph; Avraham, Karen B; Carmi, Rivka; Chalin, Catherine; El Nasser, Ziad; Hijazi, Manaf; Jebara, Rema Othman; Kanaan, Moien; Pratt, Hillel; Raad, Firas; Roth, Yehudah; Williams, A Paul; Noyek, Arnold

    This article describes a positive experience in building Arab and Israeli cooperation through health initiatives. Over the past 10 years Israeli, Jordanian, and Palestinian health professionals have worked together through the Canada International Scientific Exchange Program (CISEPO). In the initial project, nearly 17,000 Arab and Israeli newborn babies were tested for early detection of hearing loss, an important health issue for the region. The network has grown to address additional needs, including mother-child health, nutrition, infectious diseases, and youth health. Our guiding model emphasises two goals: project-specific outcomes in health improvement, and broader effects on cross-border cooperation. Lessons learned from this experience and the model provide direction for ways that health professionals can contribute to peacebuilding.

  1. Population heterogeneity promotes a preference for blind cooperation

    Science.gov (United States)

    Perez-Escudero, Alfonso; Friedman, Jonathan; Gore, Jeff

    Game theory--and common sense--recommend to carefully weigh costs and benefits before deciding on a course of action. Yet we often disapprove of people who do so, even when their actual decision benefits us. For example, we prefer people who directly agree to do us a favor over those who agree only after securing enough information to ensure that the favor will not be too costly. Why should we care about how people make their decisions, rather than just focus on the decisions themselves? Hoffman et al. (2015) have shown that such aversion to information gathering may be beneficial when it is strong enough to increase the level of cooperation. Here we show that the same type of aversion arises in heterogeneous populations, but for a different reason: individuals who seek additional information may reveal themselves to be undesirable partners, since they are less likely to cooperate in the future when conditions change. Aversion to information gathering thus facilitates preferential interactions with blind cooperators, who are more favorable partners. Due to this new mechanism the prevalence of such aversion rapidly increases with population diversity, because partner discrimination is more useful in populations which harbor partners of a more varied quality. We gratefully acknowledge funding from the Paul G. Allen Family Foundation, EMBO and Human Frontier Science Program.

  2. How to promote the regional cooperation in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Masayuki [International Affairs and Safeguards Division, Atomic Energy Bureau, Science and Technology Agency, Tokyo (Japan)

    2000-12-01

    The Tenth International Conference for Nuclear Cooperation in Asia was held in Tokyo on March 10, 1999. Representatives participated from Australia, China, Indonesia, Japan, Korea, Malaysia, the Philippines, Thailand, and Vietnam as well as IAEA as an observer. The countries reflected on the positive achievements of the past ten years and affirmed the major goals for the future, the major theme of the meeting being the evolution of the framework. Some typical cooperative activities have result in: (a) new varieties of plants with greater productivity under a range of environmental conditions (b) development and adoptions of improved analytical procedures to track air pollution in major cities where the identification of the major sources will facilitate remediation measures (c) coordinated trials for radiation therapy of cervical cancer and the development of rigorous protocols (d) training of staff in research reactor operation and in the use of research reactors for the study of new materials. The participating countries have committed to reviewing the six existing sub-categories, namely (1) utilization of research reactors, (2,3) application of radiation and radioisotope in the agriculture and the medical fields, (4) public acceptance of nuclear energy, (5) radioactive waste management, and (6) nuclear safety culture. To share knowledge on human resources development within the region and to consider measures for the further development of human resources in relevant fields, a seminar for human resources development, sponsored by Japan, will be held in Japan. The conference will be renamed as (Forum for Nuclear Cooperation in Asia) beginning with the next conference. The Forum for Nuclear Cooperation in Asia will be held in Japan and in a participating country other than Japan in alternating years. To enhance the regional nuclear cooperation activities under this framework, each participating country will register a Coordinator and Project Leaders to facilitate

  3. Older partner selection promotes the prevalence of cooperation in evolutionary games.

    Science.gov (United States)

    Yang, Guoli; Huang, Jincai; Zhang, Weiming

    2014-10-21

    Evolutionary games typically come with the interplays between evolution of individual strategy and adaptation to network structure. How these dynamics in the co-evolution promote (or obstruct) the cooperation is regarded as an important topic in social, economic, and biological fields. Combining spatial selection with partner choice, the focus of this paper is to identify which neighbour should be selected as a role to imitate during the process of co-evolution. Age, an internal attribute and kind of local piece of information regarding the survivability of the agent, is a significant consideration for the selection strategy. The analysis and simulations presented, demonstrate that older partner selection for strategy imitation could foster the evolution of cooperation. The younger partner selection, however, may decrease the level of cooperation. Our model highlights the importance of agent׳s age on the promotion of cooperation in evolutionary games, both efficiently and effectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Computational discovery of soybean promoter cis-regulatory elements for the construction of soybean cyst nematode inducible synthetic promoters

    Science.gov (United States)

    Computational methods offer great hope but limited accuracy in the prediction of functional cis-regulatory elements; improvements are needed to enable synthetic promoter design. We applied an ensemble strategy for de novo soybean cyst nematode (SCN)-inducible motif discovery among promoters of 18 co...

  5. Protection promotion and cooperation in the European semiconductor industry

    DEFF Research Database (Denmark)

    Martin, Stephen

    1996-01-01

    EC Member States' national champion policies of the 1970s were not successful in developing firms that led in their home markets, and the corresponding EC policies of the 1980s (many of which encouraged inter-European strategic alliances) were not successful in developing firms that led in the Eu......EC Member States' national champion policies of the 1970s were not successful in developing firms that led in their home markets, and the corresponding EC policies of the 1980s (many of which encouraged inter-European strategic alliances) were not successful in developing firms that led...... in the European market. Using strategies that involve world-wide cooperation, European firms are beginning to carve out secure places for themselves in what is now a world market. Joint ventures have been critical in bringing European firms up to world performance levels, but extra-European as well as intra...

  6. Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain Cooperation.

    Science.gov (United States)

    Wu, Junhui; Balliet, Daniel; Van Lange, Paul A M

    2016-04-04

    Prior theory suggests that reputation spreading (e.g., gossip) and punishment are two key mechanisms to promote cooperation in groups, but no behavioral research has yet examined their relative effectiveness and efficiency in promoting and maintaining cooperation. To examine these issues, we observed participants interacting in a four-round public goods game (PGG) with or without gossip and punishment options, and a subsequent two-round trust game (TG). We manipulated gossip as the option to send notes about other group members to these members' future partners, and punishment as the option to assign deduction points to reduce other group members' outcomes with a fee-to-fine ratio of 1:3. Findings revealed that in the four-round PGG, the option to gossip increased both cooperation and individual earnings, whereas the option to punish had no overall effect on cooperation (but a positive effect on cooperation in the last two rounds of the PGG) and significantly decreased individual earnings. Importantly, the initial option to gossip made people more trusting and trustworthy in the subsequent TG when gossip was no longer possible, compared to the no-gossip condition. Thus, we provide some initial evidence that gossip may be more effective and efficient than punishment to promote and maintain cooperation.

  7. Teacher-Community Cooperation to Promote Sustainability of ...

    African Journals Online (AJOL)

    4carolinebell@gmail.com

    establish how teachers relate with the local community and how they harness this interaction to promote sustainability of wetlands ... Participants in this research were sampled from 242 teachers who had participated in an in-service course on ..... The nature of wetlands: A handbook of wetlands in. Kenya. Nairobi: NMK ...

  8. A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Seymour, Philip A; Patel, Nisha A

    2015-01-01

    The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox......9 as cooperative inducers of a gene regulatory network that distinguishes the pancreatic from the intestinal lineage. Genetic studies demonstrate dual and cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and repression of the intestinal lineage choice. Pdx1 and Sox9 bind...... to regulatory sequences near pancreatic and intestinal differentiation genes and jointly regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9 in gene activation and repression. Our study identifies Pdx1 and Sox9 as important regulators of a transcription factor network that initiates...

  9. Collective punishment is more effective than collective reward for promoting cooperation

    Science.gov (United States)

    Gao, Lei; Wang, Zhen; Pansini, Riccardo; Li, Yao-Tang; Wang, Rui-Wu

    2015-12-01

    Collective punishment and reward are usually regarded as two potential mechanisms to explain the evolution of cooperation. Both scenarios, however, seem problematic to understand cooperative behavior, because they can raise the second-order free-rider problem and many organisms are not able to discriminate less cooperating individuals. Even though they have been proved to increase cooperation, there has been a debate about which one being more effective. To address this issue, we resort to the N-player evolutionary snowdrift game (NESG), where a collective punishment/reward mechanism is added by allowing some players to display punishment/reward towards all remaining players. By means of numerous simulations and analyses, we find that collective punishment is more effective in promoting cooperation for a relatively high initial frequency of cooperation or for a relatively small group. When the intensity of punishment exceeds a certain threshold, a stable state of full cooperation emerges for both small and large groups. In contrast, such state does not appear for large groups playing a NESG with reward mechanism. In the case of mutualistic interactions, finally, our results show the new payoff with collective punishment/reward can lead to the coexistence of cooperators and defectors when discrimination between these two is not possible.

  10. Adaptive and bounded investment returns promote cooperation in spatial public goods games.

    Directory of Open Access Journals (Sweden)

    Xiaojie Chen

    Full Text Available The public goods game is one of the most famous models for studying the evolution of cooperation in sizable groups. The multiplication factor in this game can characterize the investment return from the public good, which may be variable depending on the interactive environment in realistic situations. Instead of using the same universal value, here we consider that the multiplication factor in each group is updated based on the differences between the local and global interactive environments in the spatial public goods game, but meanwhile limited to within a certain range. We find that the adaptive and bounded investment returns can significantly promote cooperation. In particular, full cooperation can be achieved for high feedback strength when appropriate limitation is set for the investment return. Also, we show that the fraction of cooperators in the whole population can become larger if the lower and upper limits of the multiplication factor are increased. Furthermore, in comparison to the traditionally spatial public goods game where the multiplication factor in each group is identical and fixed, we find that cooperation can be better promoted if the multiplication factor is constrained to adjust between one and the group size in our model. Our results highlight the importance of the locally adaptive and bounded investment returns for the emergence and dominance of cooperative behavior in structured populations.

  11. 77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

    Science.gov (United States)

    2012-09-28

    ... to be addressed (including any information on negative effects of these differences and on the... markets and technologies. As we continue in the High Level Working Group on Jobs and Growth to examine the... approaches to standards; and An assessment of the effects of enhanced regulatory compatibility (quantified...

  12. Punitive preferences, monetary incentives and tacit coordination in the punishment of defectors promote cooperation in humans

    NARCIS (Netherlands)

    Diekmann, Andreas; Przepiorka, Wojtek|info:eu-repo/dai/nl/413317617

    2015-01-01

    Peer-punishment is effective in promoting cooperation, but the costs associated with punishing defectors often exceed the benefits for the group. It has been argued that centralized punishment institutions can overcome the detrimental effects of peer-punishment. However, this argument presupposes

  13. An upstream regulatory element confers orientation-independent enhancement of the TSG101 promoter activity in transformed cells.

    Science.gov (United States)

    Hsu, Shih-Fang; Goan, Yih-Gang; Tsai, Hsien-Yu; Lin, Yi-Ru; Liu, Rue-Tsuan; Cheng, Jiin-Tsuey

    2012-01-01

    Tumor susceptibility gene 101 (TSG101), a mammalian homologue of yeast vps23, is involved in protein sorting, vesicular trafficking and maintenance of genomic integrity. Upregulation of the TSG101 gene was found in human thyroid papillary and breast tumors. Here, we define the proximal promoter of human TSG101 at -1 to -436 by reporter assay. Intact Sp1 and MAZ binding sequences within this region are essential, and mutation of both sites eliminates proximal promoter activity implying cooperation between these two cis-elements. Chromatin immunoprecipitation and DNA affinity precipitation assay confirmed in vivo Sp1 binding on the GGGGCGGGTT sequence. MAZ protein was essential for TSG101 promoter activity because its knockdown using siRNA decreased reporter activity. An upstream regulatory element (URE) at the -1280 to -1757 region was identified to confer the orientation-independent enhancement of the promoter activity in transformed COS-1, ARO and WRO cell lines but not in a normal thyroid FRTL cell line. The sequence of this URE region contains putative binding sites for thyroid transcription factor 2 (TTF-2) and thyroid hormone receptor (T3R), which might be relevant to differential regulation of TSG101 promoter activity in transformed and primary cells.

  14. Promotion of cooperation induced by discriminators in the spatial multi-player donor-recipient game

    Science.gov (United States)

    Cui, Guang-Hai; Wang, Zhen; Ren, Jian-Kang; Lu, Kun; Li, Ming-Chu

    2016-11-01

    Although the two-player donor-recipient game has been used extensively in studying cooperation in social dilemmas, the scenario in which a donor can simultaneously donate resources to multiple recipients is also common in human societies, economic systems, and social networks. This paper formulates a model of the multi-player donor-recipient game considering a multi-recipient scenario. The promotion of cooperation is also studied by introducing a discriminative cooperation strategy into the game, which donates resources to recipients in proportion to their previous donations with a cost for the collection of information. The evolutionary dynamics of individual strategies are explored in homogeneous and heterogeneous scenarios by leveraging spatial evolutionary game theory. The results show that in a homogeneous scenario, defectors can dominate the network at the equilibrium state only when the cost-to-benefit ratio (R) of donated resources is large. In a heterogeneous scenario, three strategies can coexist all the time within the range of R that was studied, and the promotion of cooperation is more effective when the values of R are smaller. Results from a single node evolution and the formation of local patterns of interaction are provided, and it is analytically shown that discriminators can maintain fairness in resource donation and guarantee long-term cooperation when R is not too large.

  15. When Prevention Promotes Creativity : The Role of Mood, Regulatory Focus, and Regulatory Closure

    NARCIS (Netherlands)

    Baas, Matthijs; De Dreu, Carsten K. W.; Nijstad, Bernard A.

    Promotion-focused states generally boost creativity because they associate with enhanced activation and cognitive flexibility. With regard to prevention-focused states, research evidence is less consistent, with some findings suggesting prevention-focused states promote creativity and other findings

  16. When prevention promotes creativity: the role of mood, regulatory focus, and regulatory closure

    NARCIS (Netherlands)

    Baas, M.; de Dreu, C.K.W.; Nijstad, B.A.

    2011-01-01

    Promotion-focused states generally boost creativity because they associate with enhanced activation and cognitive flexibility. With regard to prevention-focused states, research evidence is less consistent, with some findings suggesting prevention-focused states promote creativity and other findings

  17. Inferring reputation promotes the evolution of cooperation in spatial social dilemma games.

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    Full Text Available In realistic world individuals with high reputation are more likely to influence the collective behaviors. Due to the cost and error of information dissemination, however, it is unreasonable to assign each individual with a complete cognitive power, which means that not everyone can accurately realize others' reputation situation. Here we introduce the mechanism of inferring reputation into the selection of potential strategy sources to explore the evolution of cooperation. Before the game each player is assigned with a randomly distributed parameter p denoting his ability to infer the reputation of others. The parameter p of each individual is kept constant during the game. The value of p indicates that the neighbor possessing highest reputation is chosen with the probability p and randomly choosing an opponent is left with the probability 1-p. We find that this novel mechanism can be seen as an universally applicable promoter of cooperation, which works on various interaction networks and in different types of evolutionary game. Of particular interest is the fact that, in the early stages of evolutionary process, cooperators with high reputation who are easily regarded as the potential strategy donors can quickly lead to the formation of extremely robust clusters of cooperators that are impervious to defector attacks. These clusters eventually help cooperators reach their undisputed dominance, which transcends what can be warranted by the spatial reciprocity alone. Moreover, we provide complete phase diagrams to depict the impact of uncertainty in strategy adoptions and conclude that the effective interaction topology structure may be altered under such a mechanism. When the estimation of reputation is extended, we also show that the moderate value of evaluation factor enables cooperation to thrive best. We thus present a viable method of understanding the ubiquitous cooperative behaviors in nature and hope that it will inspire further studies

  18. Inferring reputation promotes the evolution of cooperation in spatial social dilemma games.

    Science.gov (United States)

    Wang, Zhen; Wang, Lin; Yin, Zi-Yu; Xia, Cheng-Yi

    2012-01-01

    In realistic world individuals with high reputation are more likely to influence the collective behaviors. Due to the cost and error of information dissemination, however, it is unreasonable to assign each individual with a complete cognitive power, which means that not everyone can accurately realize others' reputation situation. Here we introduce the mechanism of inferring reputation into the selection of potential strategy sources to explore the evolution of cooperation. Before the game each player is assigned with a randomly distributed parameter p denoting his ability to infer the reputation of others. The parameter p of each individual is kept constant during the game. The value of p indicates that the neighbor possessing highest reputation is chosen with the probability p and randomly choosing an opponent is left with the probability 1-p. We find that this novel mechanism can be seen as an universally applicable promoter of cooperation, which works on various interaction networks and in different types of evolutionary game. Of particular interest is the fact that, in the early stages of evolutionary process, cooperators with high reputation who are easily regarded as the potential strategy donors can quickly lead to the formation of extremely robust clusters of cooperators that are impervious to defector attacks. These clusters eventually help cooperators reach their undisputed dominance, which transcends what can be warranted by the spatial reciprocity alone. Moreover, we provide complete phase diagrams to depict the impact of uncertainty in strategy adoptions and conclude that the effective interaction topology structure may be altered under such a mechanism. When the estimation of reputation is extended, we also show that the moderate value of evaluation factor enables cooperation to thrive best. We thus present a viable method of understanding the ubiquitous cooperative behaviors in nature and hope that it will inspire further studies to resolve social

  19. Outsource Power, Import Safety? Challenges and Opportunities of the U.S.-China Food Safety Regulatory Cooperation.

    Science.gov (United States)

    Lin, Ching-Fu

    The United States has a high stake in China’s serious food safety problem, as food products of Chinese origin have dominated the U.S. food market in numerous areas and continue to grow. The conclusion of the U.S.-China Food Safety Agreement (“the Agreement”) has allowed FDA to strengthen regulatory cooperation with its Chinese counterpart in various aspects. The Agreement also paves the way for the implementation of the new regulatory tools incorporated in FSMA, especially in the cross-border context. However, both the Agreement and FSMA have certain crucial limitations that may create future hurdles to effective implementation in the U.S.-China cooperation. This paper therefore endeavors to first examine China’s governance challenges over food safety, with a focus on the 2009 Food Safety Law, the 2015 Amendment, and the fundamental problem of “thin” rule of law. This paper moves to analyze the U.S.-China Food Safety Agreement, reviewing the agreement’s strengths and weaknesses. It further assesses FSMA’s innovative institutional design to regulate imported food products and its limitations. However, both the U.S.-China Food Safety Agreement and FSMA arguably create a regulatory dilemma for FDA when addressing imported food safety, due to structural mismatch between the broad scope of power granted to FDA and the long chain of power outsourcing to governments or private companies as primary “regulators.” Neither the Agreement nor FSMA give FDA adequate capacity to closely oversee such “agents” along the chain of power outsourcing. Framing the U.S.-China food safety cooperation as a multilayer structure that “outsources power” to “import safety,” this paper concludes by stressing the need for a robust accountability and effective mechanism for U.S.-China food safety cooperation.

  20. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Directory of Open Access Journals (Sweden)

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  1. Regulatory focus in the life story: prevention and promotion as expressed in three layers of personality.

    Science.gov (United States)

    Manczak, Erika M; Zapata-Gietl, Claudia; McAdams, Dan P

    2014-01-01

    Regulatory Focus Theory (Higgins, 1997) outlines the ways in which people attempt to achieve the presence of positive outcomes (promotion) or preserve the absence of negative outcomes (prevention), suggesting that individuals may differ in chronic orientations. The present work examines regulatory outlooks within a multilayered model of personality composed of dispositional traits, characteristic goals, and life stories (narrative identity). Foregrounding the concept of narrative identity, the current study investigates how narrative themes of prevention and promotion relate to regulatory focus as expressed in dispositional traits and characteristic goals and explores the relative contribution of each layer of personality to psychological well-being and physical health. The findings suggest that dispositional traits, personal goals, and life narratives cohere loosely around the central themes of prevention and promotion. Moreover, promotion focus across layers of personality was related to higher levels of self-reported quality of life, compared to prevention focus. Illustrating the incremental validity of different layers of personality, promotion focus in life stories independently predicted psychological health above and beyond promotion focus in dispositional traits.

  2. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Directory of Open Access Journals (Sweden)

    Daniel Meier

    Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  3. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.

    Science.gov (United States)

    Schoenfelder, Stefan; Furlan-Magaril, Mayra; Mifsud, Borbala; Tavares-Cadete, Filipe; Sugar, Robert; Javierre, Biola-Maria; Nagano, Takashi; Katsman, Yulia; Sakthidevi, Moorthy; Wingett, Steven W; Dimitrova, Emilia; Dimond, Andrew; Edelman, Lucas B; Elderkin, Sarah; Tabbada, Kristina; Darbo, Elodie; Andrews, Simon; Herman, Bram; Higgs, Andy; LeProust, Emily; Osborne, Cameron S; Mitchell, Jennifer A; Luscombe, Nicholas M; Fraser, Peter

    2015-04-01

    The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression. © 2015 Schoenfelder et al.; Published by Cold Spring Harbor Laboratory Press.

  4. Cancer nanotechnology research in the United States and China: cooperation to promote innovation.

    Science.gov (United States)

    Schneider, Julie A; Grodzinski, Piotr; Liang, Xing-Jie

    2011-01-01

    The application of nanotechnology to cancer research is a promising area for US-China cooperation. Cancer is a major public health burden in both countries, and progress in cancer nanotechnology research is increasing in several fields, including imaging, biomarker detection, and targeted drug delivery. The United States and China are international leaders in nanotechnology research, and have both launched national programs to support nanotechnology efforts in the recent past. The accelerating trend of co-authorship among US and Chinese nanotechnology researchers demonstrates that individual scientists already recognize the potential for cooperation, providing a strong platform for creating additional partnerships in pre-competitive research areas. Mechanisms that could help to enhance US-China cancer nanotechnology partnerships include: developing new programs for bi-directional training and exchange; convening workshops focused on specific scientific topics of high priority to both countries; and joint support of collaborative research projects by US and Chinese funders. In addition to the accelerating scientific progress, expanded cooperation will stimulate important dialog on regulatory, policy, and technical issues needed to lay the groundwork for US and Chinese scientists to move greater numbers of cancer nanotechnology applications into the clinic. Copyright © 2011 John Wiley & Sons, Inc.

  5. RBM20 and RBM24 cooperatively promote the expression of short enh splice variants.

    Science.gov (United States)

    Ito, Jumpei; Iijima, Masumi; Yoshimoto, Nobuo; Niimi, Tomoaki; Kuroda, Shun'ichi; Maturana, Andrés D

    2016-07-01

    PDZ-LIM protein ENH1 is a scaffold protein for protein kinases and transcriptional regulators. While ENH1 promotes the hypertrophic growth of cardiomyocytes, its short splice variant (ENH3) prevents the hypertrophic growth. The mechanism underlying the alternative splicing of enh mRNA between ENH short and long isoforms has remained unknown. Here, we found that two splicing factors, RNA-binding motif 20 (RBM20) and RNA-binding motif 24 (RBM24) together promoted the expression of short enh splice variants and bound the 5' intronic region of exon 11 containing an in-phase stop codon. In addition, expression of both RBMs is repressed by hypertrophic stimulations. Collectively, our results suggest that, in healthy conditions, RBM20 and RBM24 cooperate to promote the expression of short ENH isoforms. © 2016 Federation of European Biochemical Societies.

  6. Andrographolide Ameliorate Rheumatoid Arthritis by Promoting the Development of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Muhaimin Rifa’i

    2010-10-01

    Full Text Available Andrographolide is important material present in Andrographis paniculata. This material can promote T cell to develop into regulatory T cell, CD4+CD25+. CD4+CD25+ regulatory T (Treg cells, a component of the innate immune response, which play a key role in the maintenance of self-tolerance, have become the focus of numerous studies over the last decade. These cells have the potential to be exploited to treat autoimmune disease. These cells inhibit the immune response in an Ag-nonspecific manner, interacting with other T cells. These T cell populations actively control the properties of other immune cells by suppressing their functional activity to prevent autoimmunity but also influence the immune response to allergens as well as against tumor cells and pathogens. In this experiment we showed that active compound from Andrographis paniculata namely andrographolide can induce active regulatory T cell that has an efficacy to cure rheumatoid arthritis mice model.

  7. Quantitative Analysis of Cis-Regulatory Element Activity Using Synthetic Promoters in Transgenic Plants.

    Science.gov (United States)

    Benn, Geoffrey; Dehesh, Katayoon

    2016-01-01

    Synthetic promoters, introduced stably or transiently into plants, are an invaluable tool for the identification of functional regulatory elements and the corresponding transcription factor(s) that regulate the amplitude, spatial distribution, and temporal patterns of gene expression. Here, we present a protocol describing the steps required to identify and characterize putative cis-regulatory elements. These steps include application of computational tools to identify putative elements, construction of a synthetic promoter upstream of luciferase, identification of transcription factors that regulate the element, testing the functionality of the element introduced transiently and/or stably into the species of interest followed by high-throughput luciferase screening assays, and subsequent data processing and statistical analysis.

  8. Computational discovery of soybean promoter cis-regulatory elements for the construction of soybean cyst nematode-inducible synthetic promoters.

    Science.gov (United States)

    Liu, Wusheng; Mazarei, Mitra; Peng, Yanhui; Fethe, Michael H; Rudis, Mary R; Lin, Jingyu; Millwood, Reginald J; Arelli, Prakash R; Stewart, Charles Neal

    2014-10-01

    Computational methods offer great hope but limited accuracy in the prediction of functional cis-regulatory elements; improvements are needed to enable synthetic promoter design. We applied an ensemble strategy for de novo soybean cyst nematode (SCN)-inducible motif discovery among promoters of 18 co-expressed soybean genes that were selected from six reported microarray studies involving a compatible soybean-SCN interaction. A total of 116 overlapping motif regions (OMRs) were discovered bioinformatically that were identified by at least four out of seven bioinformatic tools. Using synthetic promoters, the inducibility of each OMR or motif itself was evaluated by co-localization of gain of function of an orange fluorescent protein reporter and the presence of SCN in transgenic soybean hairy roots. Among 16 OMRs detected from two experimentally confirmed SCN-inducible promoters, 11 OMRs (i.e. 68.75%) were experimentally confirmed to be SCN-inducible, leading to the discovery of 23 core motifs of 5- to 7-bp length, of which 14 are novel in plants. We found that a combination of the three best tools (i.e. SCOPE, W-AlignACE and Weeder) could detect all 23 core motifs. Thus, this strategy is a high-throughput approach for de novo motif discovery in soybean and offers great potential for novel motif discovery and synthetic promoter engineering for any plant and trait in crop biotechnology. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  9. My university. What I learned from the Productive Cooperative Movement to Promotion of Humanistic Family Planning.

    Science.gov (United States)

    Kunii, C

    1990-07-01

    Based on experiences with the Productive Cooperative Movement and the Parasite Control Movement in Japan, the Japanese Family Planning Movement began in April 1954. The resultant private and nonprofit Japan Family Planning Association (JFPA) followed and it served to help Japan achieve its goal of reducing fertility by promoting family planning. It did so by publishing a monthly newsletter on family planning, hosting meetings and national conventions, spreading information via the mass media, and selling contraceptives and educational materials. JFPA earned funding from these sales with no support from the government thereby establishing self dependence and freedom to speak candidly to the government. The JFPA learned that families wanted to improve their standard of living and were willing to limit family size to 2 children. After the birth rate peaked in 1955, the birth rate and the number of illegal abortions decreased. In the 1950s, JFPA joined the International Planned Parenthood Federation and subsequently learned of the problems faced by developing countries. Based on the successful reduction of fertility in Japan and a strong economic base, JFPA and the government were in a position to organize an international cooperation program for family planning. Therefore, the leader of JFPA resigned to found the Japanese Organization for International Cooperation in Family Planning which promotes family planning in developing countries via its integrated family planning, nutrition, and parasite control program. A steering committee composed of leaders from government, universities, and private organizations sets the policies for the program in each country. It is to the Japanese government's advantage to work with private organizations instead of providing all social services because they are flexible and provide administrative stability and national expenses are minimized.

  10. 78 FR 49726 - International Framework for Nuclear Energy Cooperation Finance/Regulatory/Energy Planning...

    Science.gov (United States)

    2013-08-15

    .../Energy Planning Authority Workshop October 22 in Abu Dhabi, UAE AGENCY: International Trade..., International Trade Administration. Event Description The U.S. Department of Commerce's International Trade... U.S. industry in the IFNEC Finance, Regulatory, and Energy Planning Authority Workshop, to be held...

  11. Sequence tolerance of the phage lambda PRM promoter: implications for evolution of gene regulatory circuitry.

    Science.gov (United States)

    Michalowski, Christine B; Short, Megan D; Little, John W

    2004-12-01

    Much of the gene regulatory circuitry of phage lambda centers on a complex region called the O(R) region. This approximately 100-bp region is densely packed with regulatory sites, including two promoters and three repressor-binding sites. The dense packing of this region is likely to impose severe constraints on its ability to change during evolution, raising the question of how the specific arrangement of sites and their exact sequences could evolve to their present form. Here we ask whether the sequence of a cis-acting site can be widely varied while retaining its function; if it can, evolution could proceed by a larger number of paths. To help address this question, we developed a lambda cloning vector that allowed us to clone fragments spanning the O(R) region. By using this vector, we carried out intensive mutagenesis of the P(RM) promoter, which drives expression of CI repressor and is activated by CI itself. We made a pool of fragments in which 8 of the 12 positions in the -35 and -10 regions were randomized and cloned this pool into the vector, making a pool of P(RM) variant phage. About 10% of the P(RM) variants were able to lysogenize, suggesting that the lambda regulatory circuitry is compatible with a wide range of P(RM) sequences. Analysis of several of these phages indicated a range of behaviors in prophage induction. Several isolates had induction properties similar to those of the wild type, and their promoters resembled the wild type in their responses to CI. We term this property of different sequences allowing roughly equivalent function "sequence tolerance " and discuss its role in the evolution of gene regulatory circuitry.

  12. Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.

    Science.gov (United States)

    Ma, Shisong; Snyder, Michael; Dinesh-Kumar, Savithramma P

    2017-07-17

    Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules' gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets' expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.

  13. Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.

    Science.gov (United States)

    Simmons, John K; Michalowski, Aleksandra M; Gamache, Benjamin J; DuBois, Wendy; Patel, Jyoti; Zhang, Ke; Gary, Joy; Zhang, Shuling; Gaikwad, Snehal; Connors, Daniel; Watson, Nicholas; Leon, Elena; Chen, Jin-Qiu; Kuehl, W Michael; Lee, Maxwell P; Zingone, Adriana; Landgren, Ola; Ordentlich, Peter; Huang, Jing; Mock, Beverly A

    2017-09-01

    Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared with single agents. In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared with single agents. Mice bearing plasma cell tumors lived an average of 70 days longer on combination treatment compared with single agents. A set of 37 genes cooperatively affected (34 downregulated; 3 upregulated) by the combination responded pharmacodynamically in human myeloma cell lines, xenografts, and a P493 model, and were both enriched in tumors, and correlated with prognostic markers in myeloma patient datasets. Genes downregulated by the combination were overexpressed in several untreated cancers (breast, lung, colon, sarcoma, head and neck, myeloma) compared with normal tissues. The MYC/E2F axis, identified by upstream regulator analyses and validated by immunoblots, was significantly inhibited by the drug combination in several myeloma cell lines. Furthermore, 88% of the 34 genes downregulated have MYC-binding sites in their promoters, and the drug combination cooperatively reduced MYC half-life by 55% and increased degradation. Cells with MYC mutations were refractory to the combination. Thus, integrative approaches to understand drug synergy identified a clinically actionable strategy to inhibit MYC/E2F activity and tumor cell growth in vivoMol Cancer Ther; 16(9); 2008-21. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma.

    Science.gov (United States)

    Hong, Xin; Hong, Xing-Yu; Li, Tao; He, Cheng-Yan

    2015-12-01

    Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy.

  15. A regulatory toolbox of MiniPromoters to drive selective expression in the brain

    Science.gov (United States)

    Portales-Casamar, Elodie; Swanson, Douglas J.; Liu, Li; de Leeuw, Charles N.; Banks, Kathleen G.; Ho Sui, Shannan J.; Fulton, Debra L.; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J.; Babyak, Nazar; Black, Sonia F.; Bonaguro, Russell J.; Brauer, Erich; Candido, Tara R.; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C. Y.; Chopra, Vik; Docking, T. Roderick; Dreolini, Lisa; D'Souza, Cletus A.; Flynn, Erin K.; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G.; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y.; Lim, Jonathan S.; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J.; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L.; Schmouth, Jean-François; Swanson, Magdalena I.; Tam, Bonny; Ticoll, Amy; Turner, Jenna L.; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F.; Wilson, Gary; Wong, Bibiana K. Y.; Wong, Siaw H.; Wong, Tony Y. T.; Yang, George S.; Ypsilanti, Athena R.; Jones, Steven J. M.; Holt, Robert A.; Goldowitz, Daniel; Wasserman, Wyeth W.; Simpson, Elizabeth M.

    2010-01-01

    The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination “knockins” in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5′ of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type–specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies. PMID:20807748

  16. Sodium dodecyl sulfate promoting a cooperative association process of sodium cholate with bovine serum albumin.

    Science.gov (United States)

    Schweitzer, Bianca; Felippe, Arlindo C; Dal Bó, Alexandre; Minatti, Edson; Zanette, Dino; Lopes, Antonio

    2006-06-01

    Sodium cholate (NaC) was used as a representative bile salt in the process of cooperative binding to bovine serum albumin (BSA) in a mixture with sodium dodecyl sulfate (SDS). The experiments were performed in 0.02 M Tris-HCl buffer solution (pH 7.50), in the presence of 0.1% BSA and at 25 degrees C. The aim of this study is to provide information on the performance of the BSA in the promotion of cooperative binding of sodium cholate promoted by the presence of SDS. The method used to monitor the binding was based on the analysis of the effect of SDS and NaC concentrations and their mixtures upon the fluorescence intensity of the BSA tryptophan residues. Plots of the fluorescence emission bands in terms of the A0/A ratio vs surfactant concentrations, where A0 and A represent the areas of emission bands in the presence and absence of the surfactants, respectively, were drawn in order to investigate the surfactant interaction with the protein. An alternative methodology, the specific conductivity vs surfactant concentration plots, was used, which involves mixtures of SDS and NaC to investigate the association processes, through the determination of the critical aggregation concentration (cac, when in the presence of protein) and the critical micellar concentration (cmc). The results led to a general conclusion that as the mixed micellar aggregates become richer in the bile salt monomer, the tendency to lose the reactivity with the protein increases. According to our results, a clear evidence of the predomination of BSA-SDS-NaC complexes is found only for the SDS molar fraction above approximately 0.6, and below this fraction a tendency toward free mixed micelles starts to predominate.

  17. Professional and Regulatory Infection Control Guidelines: Collaboration to Promote Patient Safety.

    Science.gov (United States)

    Clayton, Judith L; Miller, Kimberly J

    2017-09-01

    Professional organizations and regulatory agencies collaborate on infection prevention and control guidelines to support preventing and controlling infection in the surgical setting. More specifically, regulatory and accrediting agencies, professional associations, and advisory committees create and promote the use of evidence-based recommendations for preventing surgical site infections. Many agencies perform accreditation surveys to ensure compliance with these standards and guidelines. Perioperative personnel can use these resources to implement and sustain essential processes for infection prevention and control and to facilitate staff member compliance with standards, regulations, and best practices. To guide perioperative practice, it is important for nurses to understand the role of these agencies and organizations and the resources each offers to help ensure the best patient outcomes. Copyright © 2017 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  18. Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements.

    Directory of Open Access Journals (Sweden)

    Bonnie M Weasner

    2016-12-01

    Full Text Available The eyes absent (eya gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis.

  19. Footprinting the 'essential regulatory region' of the retinoblastoma gene promoter in intact human cells.

    Science.gov (United States)

    Temple, Mark D; Murray, Vincent

    2005-03-01

    The retinoblastoma tumour suppressor protein is a key cell cycle regulator. Protein-DNA interactions at the retinoblastoma (RB1) promoter, including the 'essential regulatory region', were investigated using novel DNA-targeted nitrogen mustards in intact human cells. The footprinting experiments were carried out in two different environments: in intact HeLa and K562 cells where the access of DNA-targeted probes to chromatin is affected by cellular protein-DNA interactions associated with gene regulation; and in purified DNA where their access is unencumbered by protein-DNA interactions. Using the ligation-mediated PCR (LMPCR) technique, the sites of damage were determined at base pair resolution on DNA sequencing gels. Our results demonstrate that, in intact cells, footprints were observed at the E2F, ATF and RBF1/Sp1 DNA binding motifs in the RB1 promoter. In addition, a novel footprint was observed at a previously unidentified cycle homology region (CHR) and at four uncharacterised protein-DNA binding sites. In further experiments, nitrogen mustard-treated cells were FACS sorted into G1, S and G2/M phases of the cell cycle prior to LMPCR analysis. Expression of the RB1 gene is cell cycle-regulated and footprinting studies of the promoter in FACS-sorted cells indicated that transcription factor binding at the GC box, CHR binding motif and the 'essential regulatory region' are cell cycle dependent.

  20. Regulatory elements and transcriptional control of chickenvasahomologue (CVH) promoter in chicken primordial germ cells.

    Science.gov (United States)

    Jin, So Dam; Lee, Bo Ram; Hwang, Young Sun; Lee, Hong Jo; Rim, Jong Seop; Han, Jae Yong

    2017-01-01

    Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis - and trans -regulatory elements. Studies on gene structures of chicken vasa homologue ( CVH ), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells. However, very limited studies are available on regulatory elements that control germ cell-specific expression in chicken. Therefore, we investigated the intricate regulatory mechanism(s) that governs transcriptional control of CVH . We constructed green fluorescence protein (GFP) or luciferase reporter vectors containing the various 5' flanking regions of CVH gene. From the 5' deletion and fragmented assays in chicken PGCs, we have identified a CVH promoter that locates at -316 to +275 base pair fragment with the highest luciferase activity. Additionally, we confirmed for the first time that the 5' untranslated region (UTR) containing intron 1 is required for promoter activity of the CVH gene in chicken PGCs. Furthermore, using a transcription factor binding prediction, transcriptome analysis and siRNA-mediated knockdown, we have identified that a set of transcription factors play a role in the PGC-specific CVH gene expression. These results demonstrate that cis -elements and transcription factors localizing in the 5' flanking region including the 5' UTR and an intron are important for transcriptional regulation of the CVH gene in chicken PGCs. Finally, this information will contribute to research studies in areas of reproductive biology, constructing of germ cell-specific synthetic promoter for tracing primordial germ cells as well

  1. Visual setup of logical models of signaling and regulatory networks with ProMoT

    Directory of Open Access Journals (Sweden)

    Gilles Ernst

    2006-11-01

    Full Text Available Abstract Background The analysis of biochemical networks using a logical (Boolean description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic formalism, however, they do not support logical models. Results Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats. Conclusion New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from http://www.mpi-magdeburg.mpg.de/projects/promot/.

  2. Visual setup of logical models of signaling and regulatory networks with ProMoT.

    Science.gov (United States)

    Saez-Rodriguez, Julio; Mirschel, Sebastian; Hemenway, Rebecca; Klamt, Steffen; Gilles, Ernst Dieter; Ginkel, Martin

    2006-11-17

    The analysis of biochemical networks using a logical (Boolean) description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic) formalism, however, they do not support logical models. Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats. New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from http://www.mpi-magdeburg.mpg.de/projects/promot/.

  3. 76 FR 24860 - Request for Public Comments Concerning Regulatory Cooperation Between the United States and the...

    Science.gov (United States)

    2011-05-03

    ... promote free and open trade and investment while also protecting public health and safety, the environment, intellectual property, and consumers' rights. In our trade and investment relationship with the European Union, the main impediments to greater trade and investment--and more open foreign markets for U.S. exporters...

  4. Consistent strategy updating in spatial and non-spatial behavioral experiments does not promote cooperation in social networks.

    Directory of Open Access Journals (Sweden)

    Jelena Grujić

    Full Text Available The presence of costly cooperation between otherwise selfish actors is not trivial. A prominent mechanism that promotes cooperation is spatial population structure. However, recent experiments with human subjects report substantially lower level of cooperation then predicted by theoretical models. We analyze the data of such an experiment in which a total of 400 players play a Prisoner's Dilemma on a 4×4 square lattice in two treatments, either interacting via a fixed square lattice (15 independent groups or with a population structure changing after each interaction (10 independent groups. We analyze the statistics of individual decisions and infer in which way they can be matched with the typical models of evolutionary game theorists. We find no difference in the strategy updating between the two treatments. However, the strategy updates are distinct from the most popular models which lead to the promotion of cooperation as shown by computer simulations of the strategy updating. This suggests that the promotion of cooperation by population structure is not as straightforward in humans as often envisioned in theoretical models.

  5. Promotion of cooperation induced by heterogeneity of both investment and payoff allocation in spatial public goods game

    Science.gov (United States)

    Fan, Ruguo; Zhang, Yingqing; Luo, Ming; Zhang, Hongjuan

    2017-01-01

    Heterogeneity has attracted mounting attention across multiple disciplines and is confirmed to be a greater promoter of cooperation. It is often the case that the heterogeneity always exists in investment and payoff allocation concurrently instead of separately. In addition, the factors that affect heterogeneous investment and payoff allocation are various. Inspired by this, this paper extends the previous models by incorporating heterogeneous investment and payoff allocation into the typical PGG model to further investigate the incentive mechanisms of cooperative behavior. In order to better understand the model, three different feedback mechanisms, namely the wealth-preference mechanism, the social-self-preference mechanism, and the mixed-preference mechanism, are addressed. The former two mechanisms correspond to the case of single factor and the latter corresponds to the case of double factors. The numerical simulations indicate that feedback mechanism by bridging the connections between the investment and the payoff allocation can reduce the free-rider problem. Furthermore, it is found that the cooperative frequency and average payoff perform better in the case of the mixed-preference mechanism where players will not only take previous payoff feedback as well as current investment but also their social status into their game decision-making process. In addition, full cooperation and profitability over all players can be promoted by means of increasing r or reducing α. At last, compared with another two classic networks, the extent of cooperation is promoted under the structures of the BA scale free networks.

  6. Reputation Effects in Social Networks Do Not Promote Cooperation : An Experimental Test of the Raub & Weesie Model

    NARCIS (Netherlands)

    Corten, Rense; Rosenkranz, Stephanie; Buskens, Vincent; Cook, Karen S.

    2016-01-01

    Despite the popularity of the notion that social cohesion in the form of dense social networks promotes cooperation in Prisoner's Dilemmas through reputation, very little experimental evidence for this claim exists. We address this issue by testing hypotheses from one of the few rigorous

  7. Asynchronous updates can promote the evolution of cooperation on multiplex networks

    Science.gov (United States)

    Allen, James M.; Hoyle, Rebecca B.

    2017-04-01

    We study the importance to the frequency of cooperation of the choice of updating strategies in a game played asynchronously or synchronously across layers in a multiplex network. Updating asynchronously in the public goods game leads to higher frequencies of cooperation compared to synchronous updates. How large this effect is depends on the sensitivity of the game dynamics to changes in the number of cooperators surrounding a player, with the largest effect observed when players payoffs are small. The discovery of this effect enhances understanding of cooperation on multiplex networks, and demonstrates a new way to maintain cooperation in these systems.

  8. Co-evolution of behaviour and social network structure promotes human cooperation.

    Science.gov (United States)

    Fehl, Katrin; van der Post, Daniel J; Semmann, Dirk

    2011-06-01

    The ubiquity of cooperation in nature is puzzling because cooperators can be exploited by defectors. Recent theoretical work shows that if dynamic networks define interactions between individuals, cooperation is favoured by natural selection. To address this, we compare cooperative behaviour in multiple but independent repeated games between participants in static and dynamic networks. In the latter, participants could break their links after each social interaction. As predicted, we find higher levels of cooperation in dynamic networks. Through biased link breaking (i.e. to defectors) participants affected their social environment. We show that this link-breaking behaviour leads to substantial network clustering and we find primarily cooperators within these clusters. This assortment is remarkable because it occurred on top of behavioural assortment through direct reciprocity and beyond the perception of participants, and represents a self-organized pattern. Our results highlight the importance of the interaction between ecological context and selective pressures on cooperation. © 2011 Blackwell Publishing Ltd/CNRS.

  9. Development of strategic cooperation of higher school and industrial enterprises to promote innovative development

    Directory of Open Access Journals (Sweden)

    A. O. Ermakov

    2016-01-01

    Full Text Available In this article the author analyzes the provisions of the national system of strategic planning of innovation development, of strategic planning documents within the formation of the concept of innovative development of the Russian economy, its transition to the knowledge economy Along with this, the author reviewed the current development indicators of the Russian economy and comparative analysis of world GDP and volumes of financing of scientific development of the countries of the world - the Global Competitiveness Report. The article provides the analysis and decomposition of component Pillar 12. Innovation on the innovative activity in Russia. The author gives the analysis on number of people employed in research and development personnel in the dynamics and by countries. The article presents information on the funding of scientific research in the United States, Japan, Russia, etc. as percentage of GDP and in absolute values. The article shows a consolidated list of used Russia's innovation promotion instruments (subsidies of costs for innovative projects, project financing, etc., taking account of links to documents, implementating these tools. The author considers problems of cooperation of Universities with industry in the establishment of such interaction as a factor of innovative growth in foreign literature. In the conclusion the author formulates a proposal for the intensification of research to improve forms of strategic partnership of universities and industrial enterprises on the basis of experience researchers form eastern countries, the results of applying the introduced tools at the state and regional levels and binding of adapting them to Russian realities and specifics.

  10. THE ‘MOON MAPPING’ PROJECT TO PROMOTE COOPERATION BETWEEN STUDENTS OF ITALY AND CHINA

    Directory of Open Access Journals (Sweden)

    M. Scaioni

    2016-06-01

    Full Text Available The research project ‘Moon Mapping’ has been established in 2014 between the Italian and Chinese Governments to promote cooperation and exchange between undergraduate students from both countries. The operational phase of the project started in early 2015, and will end in 2017, for a total length of three years. The main aim is to train new scholars to be able to work on different kinds of remotely-sensed data collected over the Moon surface by the Chinese space missions Chang’E-1/2. The project coordination has been assigned to the Italian Space Agency for the Italian side and to the Center of Space Exploration, China Ministry of Education, for the Chinese side. Several Chinese universities and Italian national research institutes and universities have been officially involved in this project. Six main research topics have been identified: (1 map of the solar wind ion; (2 geomorphological map of the Moon; (3 data preprocessing of Chang’E-1 mission; (4 map of element distribution; (5 establishment of 3D digital visualization system; and (6 compilation and publication of a tutorial on joint lunar mapping.

  11. International cooperation for the development of consistent and stable transportation regulations to promote and enhance safety and security

    Energy Technology Data Exchange (ETDEWEB)

    Strosnider, J. [US Nuclear Regulatory Commission, Washington, DC (United States)

    2004-07-01

    International commerce of radioactive materials crosses national boundaries, linking separate regulatory institutions with a common purpose and making it necessary for these institutions to work together in order to achieve common safety goals in a manner that does not place an undue burden on industry and commerce. Widespread and increasing use of radioactive materials across the world has led to increases in the transport of radioactive materials. The demand for consistency in the oversight of international transport has also increased to prevent unnecessary delays and costs associated with incongruent or redundant regulatory requirements by the various countries through which radioactive material is transported. The International Atomic Energy Agency (IAEA) is the authority for international regulation of transportation of radioactive materials responsible for promulgation of regulations and guidance for the establishment of acceptable methods of transportation for the international community. As such, the IAEA is seen as the focal point for consensus building between its Member States to develop consistency in transportation regulations and reviews and to ensure the safe and secure transport of radioactive material. International cooperation is also needed to ensure stability in our regulatory processes. Changes to transportation regulations should be based on an anticipated safety benefit supported by risk information and insights gained from continuing experience, evaluation, and research studies. If we keep safety as the principle basis for regulatory changes, regulatory stability will be enhanced. Finally, as we endeavour to maintain consistency and stability in our international regulations, we must be mindful of the new security challenges that lay before the international community as a result of a changing terrorist environment. Terrorism is a problem of global concern that also requires international cooperation and support, as we look for ways to

  12. Mobility can promote the evolution of cooperation via emergent self-assortment dynamics.

    Science.gov (United States)

    Joshi, Jaideep; Couzin, Iain D; Levin, Simon A; Guttal, Vishwesha

    2017-09-01

    The evolution of costly cooperation, where cooperators pay a personal cost to benefit others, requires that cooperators interact more frequently with other cooperators. This condition, called positive assortment, is known to occur in spatially-structured viscous populations, where individuals typically have low mobility and limited dispersal. However many social organisms across taxa, from cells and bacteria, to birds, fish and ungulates, are mobile, and live in populations with considerable inter-group mixing. In the absence of information regarding others' traits or conditional strategies, such mixing may inhibit assortment and limit the potential for cooperation to evolve. Here we employ spatially-explicit individual-based evolutionary simulations to incorporate costs and benefits of two coevolving costly traits: cooperative and local cohesive tendencies. We demonstrate that, despite possessing no information about others' traits or payoffs, mobility (via self-propulsion or environmental forcing) facilitates assortment of cooperators via a dynamically evolving difference in the cohesive tendencies of cooperators and defectors. We show analytically that this assortment can also be viewed in a multilevel selection framework, where selection for cooperation among emergent groups can overcome selection against cooperators within the groups. As a result of these dynamics, we find an oscillatory pattern of cooperation and defection that maintains cooperation even in the absence of well known mechanisms such as kin interactions, reciprocity, local dispersal or conditional strategies that require information on others' strategies or payoffs. Our results offer insights into differential adhesion based mechanisms for positive assortment and reveal the possibility of cooperative aggregations in dynamic fission-fusion populations.

  13. PlantPAN 2.0: an update of plant promoter analysis navigator for reconstructing transcriptional regulatory networks in plants.

    Science.gov (United States)

    Chow, Chi-Nga; Zheng, Han-Qin; Wu, Nai-Yun; Chien, Chia-Hung; Huang, Hsien-Da; Lee, Tzong-Yi; Chiang-Hsieh, Yi-Fan; Hou, Ping-Fu; Yang, Tien-Yi; Chang, Wen-Chi

    2016-01-04

    Transcription factors (TFs) are sequence-specific DNA-binding proteins acting as critical regulators of gene expression. The Plant Promoter Analysis Navigator (PlantPAN; http://PlantPAN2.itps.ncku.edu.tw) provides an informative resource for detecting transcription factor binding sites (TFBSs), corresponding TFs, and other important regulatory elements (CpG islands and tandem repeats) in a promoter or a set of plant promoters. Additionally, TFBSs, CpG islands, and tandem repeats in the conserve regions between similar gene promoters are also identified. The current PlantPAN release (version 2.0) contains 16 960 TFs and 1143 TF binding site matrices among 76 plant species. In addition to updating of the annotation information, adding experimentally verified TF matrices, and making improvements in the visualization of transcriptional regulatory networks, several new features and functions are incorporated. These features include: (i) comprehensive curation of TF information (response conditions, target genes, and sequence logos of binding motifs, etc.), (ii) co-expression profiles of TFs and their target genes under various conditions, (iii) protein-protein interactions among TFs and their co-factors, (iv) TF-target networks, and (v) downstream promoter elements. Furthermore, a dynamic transcriptional regulatory network under various conditions is provided in PlantPAN 2.0. The PlantPAN 2.0 is a systematic platform for plant promoter analysis and reconstructing transcriptional regulatory networks. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Expression of Fbxo7 in haematopoietic progenitor cells cooperates with p53 loss to promote lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Mikhail Lomonosov

    Full Text Available Fbxo7 is an unusual F box protein that augments D-type cyclin complex formation with Cdk6, but not Cdk4 or Cdk2, and its over-expression has been demonstrated to transform immortalised fibroblasts in a Cdk6-dependent manner. Here we present new evidence in vitro and in vivo on the oncogenic potential of this regulatory protein in primary haematopoietic stem and progenitor cells (HSPCs. Increasing Fbxo7 expression in HSPCs suppressed their colony forming ability in vitro, specifically decreasing CD11b (Mac1 expression, and these effects were dependent on an intact p53 pathway. Furthermore, increased Fbxo7 levels enhanced the proliferative capacity of p53 null HSPCs when they were grown in reduced concentrations of stem cell factor. Finally, irradiated mice reconstituted with p53 null, but not wild-type, HSPCs expressing Fbxo7 showed a statistically significant increase in the incidence of T cell lymphoma in vivo. These data argue that Fbxo7 negatively regulates the proliferation and differentiation of HSPCs in a p53-dependent manner, and that in the absence of p53, Fbxo7 expression can promote T cell lymphomagenesis.

  15. Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses.

    Science.gov (United States)

    Matarese, Giuseppe; Procaccini, Claudio; Menale, Ciro; Kim, Jae Geun; Kim, Jung Dae; Diano, Sabrina; Diano, Nadia; De Rosa, Veronica; Dietrich, Marcelo O; Horvath, Tamas L

    2013-04-09

    Whole-body energy metabolism is regulated by the hypothalamus and has an impact on diverse tissue functions. Here we show that selective knockdown of Sirtuin 1 Sirt1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4(+) T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. These phenomena were associated with an impaired thymic generation of forkhead box P3 (FoxP3(+)) naturally occurring regulatory T cells and their reduced suppressive capacity in the periphery, which resulted in increased delayed-type hypersensitivity responses and autoimmune disease susceptibility in mice. These observations unmask a previously unsuspected role of hypothalamic feeding circuits in the regulation of adaptive immune response.

  16. Promoting Gender Parity in Basic Education: Lessons from a Technical Cooperation Project in Yemen

    Science.gov (United States)

    Yuki, Takako; Mizuno, Keiko; Ogawa, Keiichi; Mihoko, Sakai

    2013-01-01

    Many girls are not sent to school in Yemen, despite basic education being free as well as compulsory for all children aged 6-15. Aiming to improve girls' enrollment by increasing parental and community involvement, the Japan International Cooperation Agency (JICA) offered a technical cooperation project in June 2005 called Broadening Regional…

  17. Developing Entrepreneurial and Technology Commercialization Policies to Promote Cooperative Ventures Between NIH and Industry

    Science.gov (United States)

    Rossomando, Edward F.

    2001-03-01

    The NIH has had a great influence in guiding the biological research agenda for the last half of the 20th century. This may change if the increases in research funding from the private sector that occurred in the last ten years continue into the 21st century. Ten years ago, industry supplied 55% of the US R&D funds. In 2000, industry support of R&D had increased to 76%, with industry carrying out 70% of the nations applied and 91% of its development research. Given this shift, one of the biggest challenges that NIH may face in coming years is sharing control of America's research agenda with industry. For this to occur policies that encourage cooperative ventures with industry are needed. In a unique experiment, I was invited to the National Institute of Dental and Craniofacial Research (NIDCR), one of the 25 NIH Institutes and Centers, to develop programs and policies that would promote interactions with industry. This talk will introduce the strategy and programs developed to commercialize products and technologies from basic science discoveries and introducing an entrepreneurial atmosphere within the Institute. The results of this experiment will be discussed by comparing differences between discovery-driven and customer-driven innovation. One outcome of this experience is a greater appreciation of the obstacles to introducing disruptive technologies into the market place and of the paradigms that serve as barriers to commercialization. One recommendation is that the NIDCR consider a policy that allows for some participation by industry in setting the research and training agenda of the Institute, and that a mechanism for industry input be introduced into its administrative organization.

  18. Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1.

    Directory of Open Access Journals (Sweden)

    Shoba Amarnath

    2010-02-01

    Full Text Available Immunotherapy using regulatory T cells (Treg has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that human Tregs promote the generation of myeloid dendritic cells (DC with reduced capacity to stimulate effector T cell responses. In a model of xenogeneic graft-versus-host disease (GVHD, allogeneic human DC conditioned with Tregs suppressed human T cell activation and completely abrogated posttransplant lethality. Tregs induced programmed death ligand-1 (PD-L1 expression on Treg-conditioned DC; subsequently, Treg-conditioned DC induced PD-L1 expression in vivo on effector T cells. PD-L1 blockade reversed Treg-conditioned DC function in vitro and in vivo, thereby demonstrating that human Tregs can promote immune suppression via DC modulation through PD-L1 up-regulation. This identification of a human Treg downstream cellular effector (DC and molecular mechanism (PD-L1 will facilitate the rational design of clinical trials to modulate alloreactivity.

  19. Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury.

    Science.gov (United States)

    Yang, Mu-Qing; Du, Qiang; Goswami, Julie; Varley, Patrick R; Chen, Bin; Wang, Rong-Hua; Morelli, Adrian E; Stolz, Donna B; Billiar, Timothy R; Li, Jiyu; Geller, David A

    2017-10-23

    The role and regulators of extracellular vesicles (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a GTPase known to control EVs release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain GTPases. However, the relationships among IRF-1, Rab27a, and EVs secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF-1 transduction, or IR promoted Rab27a expression and EVs secretion. Meanwhile, silencing of IRF-1 decreased Rab27a expression and EVs secretion. Rab27a silencing decreased EVs secretion and liver IR injury. Ten putative IRF-1 binding motifs in the 1,692 base pairs Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF-1 binding motifs, which were confirmed by Rab27a promoter luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on EVs surface activated neutrophil through toll like receptor 4 (TLR-4) pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. These findings provide a novel mechanism by which IRF-1 regulates Rab27a transcription and EVs secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  20. Assessing Motivation of Secondary School Students: An Analysis of Promotion and Prevention Orientations as Measured by the Regulatory Focus Questionnaire

    Science.gov (United States)

    Hodis, Flaviu A.; Hodis, Georgeta M.

    2017-01-01

    Measuring human motivation requires understanding the outcomes individuals value and the strategies they prefer to employ to attain them. Knowledge of promotion and prevention, two pivotal motivation orientations, provide key information regarding these aspects. The Regulatory Focus Questionnaire, which measures these two independent constructs,…

  1. Hunting for wealthy encounters promotes cooperation in spatial Prisoner's Dilemma games

    Science.gov (United States)

    Yang, Zhihu; Wu, Te; Li, Zhi; Wang, Long

    2013-04-01

    We consider an evolutionary Prisoner's Dilemma game on the lattice where a parameter α is employed to determine with whom individuals aspire to interact in future iterations. Specifically, for positive α, rich environments are preferentially considered when individuals hunt for new surroundings, while for negative α, the opposite holds. When α = 0, individuals adopt `random move'-like migration. The results indicate that aspiring for wealthy ambience makes cooperation survive and even thrive under certain circumstances. Moreover, there exist the optimal population densities that most uphold cooperation. We also investigate the expansion of cooperators. And the discovery of utmost salience is that cooperators can spontaneously break out for the population consisting of full defectors in the presence of strategy mutation. Our results relax the requirements for cooperation to outbreak and suggest that spying into others' strategies is not always necessary for the cooperation to burst. Finally, we deepen our studies by exploring the situation that each individual has an independent α and find that the fate of evolution is mainly determined by the population composition in this scenario.

  2. A Virtual Platform for Improving Coordination and Promoting Cooperation on Traffic Safety

    Directory of Open Access Journals (Sweden)

    Rabee Mohamed Reffat

    2014-03-01

    Full Text Available Successful management of traffic safety requires effective community participation in the process of traffic awareness, planning and management along with the executive bodies concerned with traffic planning and management. Just as important to reinforcing a shared vision among people and management bodies is the idea of people participation in decision-making. There is a strong need for cooperation among traffic users, planners and managers. Traffic users play a significant role in running the traffic and have been vocal about management issues. Users should be encouraged to be as involved and active as possible in all decisions that affect their traffic safety. Community Corporations go further and encourage participation by forming user organizations. Encouraging user participation also requires training for oversight and conflict resolution, in order to work through unresolved problems. It is also as important that users should try out their ideas in an open exchange, see how the ideas fare; and hopefully, the best ones will survive and users learn through each other. Therefore, there is a great need to provide users, traffic planners and managers with a platform that fosters such activities and allows traffic users to discuss, report and document their views, events, experiences related to their traffic safety, i.e. report on faults, cracks, breakdown, damages, etc. Making a good use of such data can substantially assist in improving the operation and management of traffic safety. Virtual environments can provide traffic users, planners and managers with an atmosphere to participate in a computer generated world. Virtual environments run on multiple processes in which information are shared among processes. Traffic users, planners and managers will be able to visualize and navigate the virtual traffic modeled in distributed virtual environments. Traffic management is essential to achieve better reliability and availability of traffic safety

  3. Competitive mindsets, creativity, and the role of regulatory focus

    NARCIS (Netherlands)

    Bittner, Jenny; Heidemeier, Heike

    2013-01-01

    We examined how regulatory focus and intentions to compete rather than cooperate with group members relate to creativity. Study 1 showed that a promotion focus (i.e., a focus on ideals) activated a cooperative mindset, whereas a prevention focus (i.e., a focus on responsibilities) activated a

  4. Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2.

    Science.gov (United States)

    Satoh, Tetsurou; Ishizuka, Takahiro; Tomaru, Takuya; Yoshino, Satoshi; Nakajima, Yasuyo; Hashimoto, Koshi; Shibusawa, Nobuyuki; Monden, Tsuyoshi; Yamada, Masanobu; Mori, Masatomo

    2009-07-01

    The 26S proteasome, which degrades ubiquitinated proteins, appears to contribute to the cyclical loading of androgen receptor (AR) to androgen response elements of target gene promoters; however, the mechanism whereby the 26S proteasome modulates AR recruitment remains unknown. Using yeast two-hybrid screening, we previously identified Tat-binding protein-1 (TBP-1), an adenosine triphosphatase of 19S regulatory particles of the 26S proteasome, as a transcriptional coactivator of thyroid hormone receptor. Independently, TBP-1-interacting protein (TBPIP) was also identified as a coactivator of several nuclear receptors, including AR. Here, we investigated whether TBP-1 could interact with and modulate transcriptional activation by AR cooperatively with TBPIP. TBP-1 mRNA was ubiquitously expressed in human tissues, including the testis and prostate, as well as in LNCaP cells. TBP-1 directly bound TBPIP through the amino-terminal domain possessing the leucine zipper structure. AR is physically associated with TBP-1 and TBPIP in vitro and in LNCaP cells. TBP-1 similarly and additively augmented AR-mediated transcription upon coexpression with TBPIP, and the ATPase domain, as well as leucine zipper structure in TBP-1, was essential for transcriptional enhancement. Overexpression of TBP-1 did not alter AR protein and mRNA levels. In the chromatin immunoprecipitation assay, TBP-1 was transiently recruited to the proximal androgen response element of the prostate-specific antigen gene promoter in a ligand-dependent manner in LNCaP cells. These findings suggest that a component of 19S regulatory particles directly binds AR and might participate in AR-mediated transcriptional activation in cooperation with TBPIP.

  5. Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

    Science.gov (United States)

    Doñas, Cristian; Fritz, Macarena; Manríquez, Valeria; Tejón, Gabriela; Bono, María Rosa; Loyola, Alejandra; Rosemblatt, Mario

    2013-01-01

    Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells. PMID:23737814

  6. Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Cristian Doñas

    2013-01-01

    Full Text Available Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3 is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.

  7. Conditional Cooperativity in Toxin-Antitoxin Regulation Prevents Random Toxin Activation and Promotes Fast Translational Recovery

    DEFF Research Database (Denmark)

    Cataudella, Ilaria; Trusina, Ala; Sneppen, Kim

    2012-01-01

    Many toxin–antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called ‘conditional cooperativity’ as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship...... with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA...... such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated....

  8. Regulatory fit effects on children's responses to healthy eating promotion: an experiment testing message and celebrity fit.

    Science.gov (United States)

    Cheng, Benjamin Ka Lun

    2015-01-01

    This study adopts the regulatory fit theory and examines the effects of the celebrity and message fit on children's responses to the promotion of healthy eating. A 2 × 2 experiment was conducted with 87 Hong Kong children ages 11 to 16. The results showed that a regulatory fit between the celebrity focus and the message focus yielded a better affective response. Specifically, children found a poster ad more convincing, liked it more, held more positive feelings, and found the poster ad more interesting in the fit conditions. Implications and future research directions were discussed.

  9. Promotion of cooperation induced by a self-questioning update rule in the spatial traveler's dilemma game

    Science.gov (United States)

    Miao, Qing; Wang, Juan; Hu, Meng-long; Zhang, Fan; Zhang, Qiu-shi; Xia, Cheng-yi

    2014-01-01

    In sociology and economics, evolutionary game theory has provided a powerful framework to illustrate the social dilemma's problems, and many evolutionary game models are presented, such as prisoner's dilemma game, snowdrift game, public goods game, and so on. In this paper, however, we focus on another typical pair-wise game model: Traveler's Dilemma Game (TDG), which has been deeply investigated in economics, but less attention has been paid to this topic within the physics community. We mainly discuss the influence of strategy update rules on the evolution of cooperation in the spatial TDG, and in detail explore the role of a novel self-questioning or self-learning update mechanism in the evolution of cooperation of the TDG model on the square lattice. In our self-questioning rule, each player does not imitate the strategy state of his or her nearest neighbors and simply plays the traveler's dilemma games twice with nearest neighbors: one is to calculate the actual payoff in the current game round; the other is to perform a virtual game which is used to obtain an intangible payoff if he or she adopts another random strategy. Then, the focal player decides to keep the current strategy or to change into that virtual strategy according to the Fermi-like dynamics. A great number of Monte Carlo simulations indicate that our self-questioning rule is a low information game decision-making mechanism which can greatly promote the evolution of cooperation for some specific conditions in the spatial TDG model. Furthermore, this novel rule can also be applied into the prisoner's dilemma game, and likewise the behavior of cooperation can be largely enhanced. Our results are of high importance to analyze and understand the emergence of cooperation within many real social and economical systems.

  10. Cooperative Games as an Intervention to Promote Cross-racial Acceptance.

    Science.gov (United States)

    Rogers, Marian; And Others

    1981-01-01

    More cross-racial interaction was found among boys because they participate in more team sports. Cooperative games have a strong potential for facilitating social acceptance among desegregated elementary school girls. Observations of cross-racial prosocial and antagonistic interactions revealed the practical value of games for increasing…

  11. Hidden Paths from Morality to Cooperation: Moral Judgments Promote Trust and Trustworthiness

    Science.gov (United States)

    Simpson, Brent; Harrell, Ashley; Willer, Robb

    2013-01-01

    Classic sociological solutions to cooperation problems were rooted in the moral judgments group members make about one another's behaviors, but more recent research on prosocial behaviors has largely ignored this foundational work. Here, we extend theoretical accounts of the social effect of moral judgments. Where scholars have emphasized the…

  12. Pair bond endurance promotes cooperative food defense and inhibits conflict in coral reef butterflyfishes

    KAUST Repository

    Nowicki, Jessica P

    2017-11-14

    Pair bonding is generally linked to monogamous mating systems, where the reproductive benefits of extended mate guarding and/or of bi-parental care are considered key adaptive functions. However, in some species, including coral reef butterflyfishes (f. Chaetodonitidae), pair bonding occurs in sexually immature and homosexual partners, and in the absence of parental care, suggesting there must be non-reproductive adaptive benefits of pair bonding. Here, we examined whether pair bonding butterflyfishes cooperate in defense of food, conferring direct benefits to one or both partners. Pairs of Chaetodon lunulatus and C. baronessa use contrasting cooperative strategies. In C. lunulatus, both partners mutually defend their territory, while in C. baronessa, males prioritize territory defence; conferring improvements in feeding and energy reserves in both sexes relative to solitary counterparts. We further demonstrate that partner fidelity contributes to this function by showing that re-pairing invokes intra-pair conflict and inhibits cooperatively-derived feeding benefits, and that partner endurance is required for these costs to abate. Overall, our results suggest that in butterflyfishes, pair bonding enhances cooperative defense of prey resources, ultimately benefiting both partners by improving food resource acquisition and energy reserves.

  13. Impact of European Territorial Cooperation (ETC on the promotion and use of solar energy in the Mediterranean

    Directory of Open Access Journals (Sweden)

    J. Gomez Prieto

    2016-01-01

    Full Text Available The aim of this paper is to assess the contribution of European Territorial Cooperation (ETC programmes operating in the Mediterranean area as a supporting way to achieve the renewable energy objectives established in European Union Directive 2009/28/EC. It addresses a combination of impact and thematic assessment applied to projects tackling solar energy over the period 2007–13. Observations indicate that although not always measurable, ETC contributions to the use and promotion of solar energy in the Mediterranean represent a key step forward in higher deployment. The paper also suggest alternatives to improve projects’ outputs to be delivered in the new cycle 2014–20.

  14. Interferon Regulatory Factor 6 Promotes Keratinocyte Differentiation in Response to Porphyromonas gingivalis.

    Science.gov (United States)

    Huynh, Jennifer; Scholz, Glen M; Aw, Jiamin; Reynolds, Eric C

    2017-05-01

    We recently demonstrated that the expression of the interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogen Porphyromonas gingivalis Here, we have established that IRF6 promotes the differentiation of oral keratinocytes in response to P. gingivalis This was evidenced by the IRF6-dependent upregulation of specific markers of keratinocyte terminal differentiation (e.g., involucrin [IVL] and keratin 13 [KRT13]), together with additional transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 (GRHL3) and Ovo-like zinc finger 1 (OVOL1). We have previously established that the transactivator function of IRF6 is activated by receptor-interacting protein kinase 4 (RIPK4). Consistently, the silencing of RIPK4 inhibited the stimulation of IVL, KRT13, GRHL3, and OVOL1 gene expression. IRF6 was shown to also regulate the stimulation of transglutaminase-1 (TGM1) gene expression by P. gingivalis, as well as that of small proline-rich proteins (e.g., SPRR1), which are covalently cross-linked by TGM1 to other proteins, including IVL, during cornification. The expression of the tight junction protein occludin (OCLN) was found to also be upregulated in an IRF6-dependent manner. IRF6 was demonstrated to be important for the barrier function of oral keratinocytes; specifically, silencing of IRF6 increased P. gingivalis-induced intercellular permeability and cell invasion. Taken together, our findings potentially position IRF6 as an important mediator of barrier defense against P. gingivalis. Copyright © 2017 American Society for Microbiology.

  15. IL2 Variant Circumvents ICOS+ Regulatory T-cell Expansion and Promotes NK Cell Activation.

    Science.gov (United States)

    Sim, Geok Choo; Liu, Chengwen; Wang, Ena; Liu, Hui; Creasy, Caitlin; Dai, Zhimin; Overwijk, Willem W; Roszik, Jason; Marincola, Francesco; Hwu, Patrick; Grimm, Elizabeth; Radvanyi, Laszlo

    2016-11-01

    Clinical responses to high-dose IL2 therapy are limited due to selective expansion of CD4+CD25+Foxp3+ T-regulatory cells (Treg), especially ICOS+ Tregs, rather than natural killer (NK) cells and effector T cells. These ICOS+ Tregs are highly suppressive and constitutively express high levels of IL2Rα (CD25) and CD39. Here, we characterized the effect of a mutant form of IL2 (F42K), which preferentially binds to the lower affinity IL2Rβγ with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets. Unlike wild-type (WT) IL2, F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs in peripheral blood mononuclear cells (PBMC) from healthy controls and melanoma patients. Instead, it promoted the expansion of CD16+CD56+ NK cells and CD56hiCD16- NK cell subsets in both short- and long-term cultures, with enhanced Bcl-2 expression. Stimulation of PBMCs with F42K induced expression of more NK cell activation molecules, such as NKp30, NKp44, DNAM-1, NKG2D, 4-1BB/CD137, and Tim-3, than WT IL2. F42K induced greater upregulation of TRAIL, and NK-mediated cytolytic activity was increased against both autologous and HLA-mismatched melanoma cells compared with WT IL2. Gene expression analysis revealed distinct gene expression profiles stimulated by F42K, WT IL2, and IL15. F42K therapy in vivo also induced a dramatic reduction in the expansion of ICOS+ Tregs, promoted NK cell expansion, and inhibited melanoma tumor growth more efficiently than WT IL2 and more effectively than anti-CTLA-4. Our findings suggest that F42K could be a potential substitute for WT IL2 as a cytokine therapy for cancer. Cancer Immunol Res; 4(11); 983-94. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Reputation Effects in Social Networks Do Not Promote Cooperation: An Experimental Test of the Raub & Weesie Model.

    Science.gov (United States)

    Corten, Rense; Rosenkranz, Stephanie; Buskens, Vincent; Cook, Karen S

    2016-01-01

    Despite the popularity of the notion that social cohesion in the form of dense social networks promotes cooperation in Prisoner's Dilemmas through reputation, very little experimental evidence for this claim exists. We address this issue by testing hypotheses from one of the few rigorous game-theoretic models on this topic, the Raub & Weesie model, in two incentivized lab experiments. In the experiments, 156 subjects played repeated two-person PDs in groups of six. In the "atomized interactions" condition, subjects were only informed about the outcomes of their own interactions, while in the "embedded" condition, subjects were informed about the outcomes of all interactions in their group, allowing for reputation effects. The design of the experiments followed the specification of the RW model as closely as possible. For those aspects of the model that had to be modified to allow practical implementation in an experiment, we present additional analyses that show that these modifications do not affect the predictions. Contrary to expectations, we do not find that cooperation is higher in the embedded condition than in the atomized interaction. Instead, our results are consistent with an interpretation of the RW model that includes random noise, or with learning models of cooperation in networks.

  17. Reputation Effects in Social Networks Do Not Promote Cooperation: An Experimental Test of the Raub & Weesie Model.

    Directory of Open Access Journals (Sweden)

    Rense Corten

    Full Text Available Despite the popularity of the notion that social cohesion in the form of dense social networks promotes cooperation in Prisoner's Dilemmas through reputation, very little experimental evidence for this claim exists. We address this issue by testing hypotheses from one of the few rigorous game-theoretic models on this topic, the Raub & Weesie model, in two incentivized lab experiments. In the experiments, 156 subjects played repeated two-person PDs in groups of six. In the "atomized interactions" condition, subjects were only informed about the outcomes of their own interactions, while in the "embedded" condition, subjects were informed about the outcomes of all interactions in their group, allowing for reputation effects. The design of the experiments followed the specification of the RW model as closely as possible. For those aspects of the model that had to be modified to allow practical implementation in an experiment, we present additional analyses that show that these modifications do not affect the predictions. Contrary to expectations, we do not find that cooperation is higher in the embedded condition than in the atomized interaction. Instead, our results are consistent with an interpretation of the RW model that includes random noise, or with learning models of cooperation in networks.

  18. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

    DEFF Research Database (Denmark)

    Nielsen, Christian Thomas Friberg; Huttner, Diana; Bizard, Anna H

    2015-01-01

    PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural......-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis....

  19. Selfish third parties act as peacemakers by transforming conflicts and promoting cooperation.

    Science.gov (United States)

    Halevy, Nir; Halali, Eliran

    2015-06-02

    The tremendous costs of conflict have made humans resourceful not only at warfare but also at peacemaking. Although third parties have acted as peacemakers since the dawn of history, little is known about voluntary, informal third-party intervention in conflict. Here we introduce the Peacemaker Game, a novel experimental paradigm, to model and study the interdependence between disputants and third parties in conflict. In the game, two disputants choose whether to cooperate or compete and a third party chooses whether or not to intervene in the conflict. Intervention introduces side payments that transform the game disputants are playing; it also introduces risk for the third party by making it vulnerable to disputants' choices. Six experiments revealed three robust effects: (i) The mere possibility of third-party intervention significantly increases cooperation in interpersonal and intergroup conflicts; (ii) reducing the risk to third parties dramatically increases intervention rates, to everyone's benefit; and (iii) disputants' cooperation rates are consistently higher than third parties' intervention rates. These findings explain why, how, and when self-interested third parties facilitate peaceful conflict resolution.

  20. Punishment in the form of shared cost promotes altruism in the cooperative dilemma games.

    Science.gov (United States)

    Zhang, Chunyan; Zhu, Yuying; Chen, Zengqiang; Zhang, Jianlei

    2017-05-07

    One phenomenon or social institution often observed in multi-agent interactions is the altruistic punishment, i.e. the punishment of unfair behavior by others at a personal cost. Inspired by the works focusing on punishment and the intricate mechanism behind it, we theoretically study the strategy evolution in the framework of two-strategy game models with the punishment on defectors, moreover, the cost of punishing will be evenly shared among the cooperators. Theoretical computations suggest that larger punishment on defectors or smaller punishment cost incurred by cooperators will enhance the fixation of altruistic cooperation in the population. Through the replicate dynamics, the group size of the randomly selected individuals from the sufficiently large population will notably affect the strategy evolution in populations nested within a dilemma. By theoretical modeling the concept of shared cost for punishment from one point of view, our findings underscore the importance of punishment with shared cost as a factor in real-life decisions in an evolutionary game context. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pricing, Carbon Emission Reduction, Low-Carbon Promotion and Returning Decision in a Closed-Loop Supply Chain under Vertical and Horizontal Cooperation

    Directory of Open Access Journals (Sweden)

    Hui Li

    2017-11-01

    Full Text Available In this paper, we examine the influences of vertical and horizontal cooperation models on the optimal decisions and performance of a low-carbon closed-loop supply chain (CLSC with a manufacturer and two retailers, and study optimal operation in the competitive pricing, competitive the low-carbon promotion, the carbon emission reduction, the used-products collection and the profits. We consider the completely decentralized model, M-R vertical cooperation model, R-R horizontal cooperation model, M-R-R vertical and horizontal cooperation model and completely centralized model, and also identify the optimal decision results and profits. It can be observed from a systematic comparison and numerical analysis that the completely centralized model is best in all optimal decision results among all models. In semi-cooperation, the M-R vertical cooperation model is positive, the R-R horizontal cooperation model is passive, and the positivity of the M-R-R vertical and horizontal cooperation model decreases with competitive intensity increasing in the used-products returning, carbon emissions reduction level, low-carbon promotion effort and the profits of the manufacturer and the entire supply chain.

  2. COOP+ project: Promoting the cooperation of international Research Infrastructures to address global environmental challenges.

    Science.gov (United States)

    Bonet-García, F.; Järvi, L.; Asmi, A.; Suárez-Muñoz, M.

    2016-12-01

    Humanity must face enormous environmental challenges including biodiversity decline, climate change, ocean acidification, sea level rise and overpopulation. The research infrastructures (RIs) created in the last decades worldwide cover a wide range of spatial and thematic scales and collect information about the functioning of Earth ecosystems. However, we need to go one step forward: understand and simulate the functioning of the Earth as a complex system in a global change scenario. Cooperation among international RIs as well as multidisciplinary work are mandatory to achieve this challenging objective. COOP+ (EU Horizon 2020 project) aims to strengthen the links and coordination of European environmental RIs with their international counterparts. COOP+ will create cooperation threads among international research infrastructures using environmental Global Challenges (GCs) as thematic guidelines. These GCs are polyhedral and sometimes wicked problems that threaten the sustainability of our modern societies from a social and environmental perspective. This contribution describes how COOP+ uses GCs as guidelines to foster cooperation among RIs. First we have created an open survey to collect ideas about GCs within the different scientific communities. We present the structure of this survey as well as the preliminary information that it contains. The survey will be accepting responses during the project life (September 2018). We also describe the structure of a template that will be used to collaboratively characterize some selected GCs under the point of view of RIs. The main idea is to assess how RIs can be useful to address global environmental problems. We encourage all scientists related to RIs communities to participate in this process.

  3. Resistance of Foxp3+ regulatory T cells to Nur77-induced apoptosis promotes allograft survival.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available The NR4A nuclear receptor family member Nur77 (NR4A1 promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by approximately 80% compared to wild-type (WT mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT and secondary lymphoid organs (40-50% of CD4+Foxp3+ T cells vs. 7-8% in WT of Nur77 transgenic (Nur77Tg mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival.

  4. The Kinase mTORC1 Promotes the Generation and Suppressive Function of Follicular Regulatory T Cells.

    Science.gov (United States)

    Xu, Lifan; Huang, Qizhao; Wang, Haoqiang; Hao, Yaxing; Bai, Qiang; Hu, Jianjun; Li, Yiding; Wang, Pengcheng; Chen, Xiangyu; He, Ran; Li, Bingshou; Yang, Xia; Zhao, Tingting; Zhang, Yanyan; Wang, Yifei; Ou, Juanjuan; Liang, Houjie; Wu, Yuzhang; Zhou, Xinyuan; Ye, Lilin

    2017-09-19

    Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation. Mechanistically, mTORC1-mediated phosphorylation of the transcription factor STAT3 induced the expression of the transcription factor TCF-1 by promoting STAT3 binding to the Tcf7 5'-regulatory region. Subsequently, TCF-1 bound to the Bcl6 promoter to induce Bcl6 expression, which launched the Tfr cell differentiation program. Thus, mTORC1 initiates Tfr cell differentiation by activating the TCF-1-Bcl-6 axis during immunization or infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Democracy Promotion at a Local Level : Experiences, Perspectives and Policy of Swiss International Cooperation

    Directory of Open Access Journals (Sweden)

    Martin Dahinden

    2014-09-01

    Full Text Available I would like to thank Andrea Iff and Marco Pfister from swisspeace, who were asked by the SDC’s Analysis and Policy Division to write a discussion paper on the SDC’s democracy promotion. The project further received advice and drew extensively from dlgn’s (SDC Decentralisation and Local Governance Network work. The results of dlgn’s work are accessible in full detail on the dlgn website, http://www.sdc-decentralization.net.What is democracy promotion? Today, we are witnessing a new wave of i...

  6. Stern-judging: A simple, successful norm which promotes cooperation under indirect reciprocity.

    Directory of Open Access Journals (Sweden)

    Jorge M Pacheco

    2006-12-01

    Full Text Available We study the evolution of cooperation under indirect reciprocity, believed to constitute the biological basis of morality. We employ an evolutionary game theoretical model of multilevel selection, and show that natural selection and mutation lead to the emergence of a robust and simple social norm, which we call stern-judging. Under stern-judging, helping a good individual or refusing help to a bad individual leads to a good reputation, whereas refusing help to a good individual or helping a bad one leads to a bad reputation. Similarly for tit-for-tat and win-stay-lose-shift, the simplest ubiquitous strategies in direct reciprocity, the lack of ambiguity of stern-judging, where implacable punishment is compensated by prompt forgiving, supports the idea that simplicity is often associated with evolutionary success.

  7. Promoting gender parity in basic education: Lessons from a technical cooperation project in Yemen

    Science.gov (United States)

    Yuki, Takako; Mizuno, Keiko; Ogawa, Keiichi; Mihoko, Sakai

    2013-06-01

    Many girls are not sent to school in Yemen, despite basic education being free as well as compulsory for all children aged 6-15. Aiming to improve girls' enrolment by increasing parental and community involvement, the Japan International Cooperation Agency (JICA) offered a technical cooperation project in June 2005 called Broadening Regional Initiative for Developing Girls' Education (BRIDGE). Phase 1 of this project ran for three and a half years, piloting a participatory school management model supported by school grants in six districts of the Taiz Governorate in the Southwest of Yemen. To find out how successful this approach has been in a traditional society, the authors of this paper analysed the gender parity index (GPI) of the project's pilot schools. Based on data collected at three points in time (in the initial and final years of the project, and two years after the project's end), their findings suggest that interventions in school management which strongly emphasise girls' education can be effective in improving gender parity rather quickly, regardless of the schools' initial conditions. However, the authors also observe that the pilot schools' post-project performance in terms of gender parity is mixed. While the local government allocated budgets for school grants to all pilot schools even after the project's end, training and monitoring activities were cut back. The authors further observe that the variation in performance appears to be significantly correlated with school leaders' initial perceptions of gender equality and with the number of female teachers employed. These findings point to the importance of providing schools with continuous long-term guidance and of monitoring those which implement school improvement programmes.

  8. Promoting Early Adolescents' Achievement and Peer Relationships: The Effects of Cooperative, Competitive, and Individualistic Goal Structures

    Science.gov (United States)

    Roseth, Cary J.; Johnson, David W.; Johnson, Roger T.

    2008-01-01

    Emphasizing the developmental need for positive peer relationships, in this study the authors tested a social-contextual view of the mechanisms and processes by which early adolescents' achievement and peer relationships may be promoted simultaneously. Meta-analysis was used to review 148 independent studies comparing the relative effectiveness of…

  9. Cooperative Learning and the Appropriation of Procedural Knowledge by Primary School Children.

    Science.gov (United States)

    Rojas-Drummond, Sylvia; Hernandez, Gerardo; Velez, Maricela; Villagran, Gabina

    1998-01-01

    The development and promotion of self-regulatory strategies for comprehending and learning from text were studied in 19 9-year olds using cooperative learning. The experimental group exposed to repeated reading experiences within the cooperative learning teams showed marked development of strategies for dealing with texts in comparison with the…

  10. An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers.

    Science.gov (United States)

    Morita, Hideaki; Arae, Ken; Unno, Hirotoshi; Miyauchi, Kousuke; Toyama, Sumika; Nambu, Aya; Oboki, Keisuke; Ohno, Tatsukuni; Motomura, Kenichiro; Matsuda, Akira; Yamaguchi, Sachiko; Narushima, Seiko; Kajiwara, Naoki; Iikura, Motoyasu; Suto, Hajime; McKenzie, Andrew N J; Takahashi, Takao; Karasuyama, Hajime; Okumura, Ko; Azuma, Miyuki; Moro, Kazuyo; Akdis, Cezmi A; Galli, Stephen J; Koyasu, Shigeo; Kubo, Masato; Sudo, Katsuko; Saito, Hirohisa; Matsumoto, Kenji; Nakae, Susumu

    2015-07-21

    House dust mite-derived proteases contribute to allergic disorders in part by disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to protease allergens, can induce innate-type airway eosinophilia by activating natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type airway eosinophilia. However, we found that MC-deficient Kit(W-sh/W-sh) mice exhibited exacerbated protease-induced lung inflammation associated with reduced numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain- or IL-33-induced airway eosinophilia. We have thus identified a unique anti-inflammatory pathway that can limit induction of innate-type allergic airway inflammation mediated by NH cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Cooperative Learning that Includes Students with Disabilities: An Effective Teaching Strategy, Cooperative Learning Promotes Student Interaction, Benefiting Students with and without Disabilities

    Science.gov (United States)

    Grenier, Michelle; Dyson, Ben; Yeaton, Pat

    2005-01-01

    In this article, cooperative learning is discussed as an instructional strategy that encourages students to work together and that enhances motivation for learning (Johnson & Johnson, 1989; Polloway, Patton, & Serna, 2001). Cooperative learning is presented through the depiction of a scenario inspired by observations made during a research…

  12. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury.

    Science.gov (United States)

    Trakhtenberg, Ephraim F; Li, Yiqing; Feng, Qian; Tso, Janice; Rosenberg, Paul A; Goldberg, Jeffrey L; Benowitz, Larry I

    2017-10-27

    The inability of axons to regenerate over long-distances in the central nervous system (CNS) limits the recovery of sensory, motor, and cognitive functions after various CNS injuries and diseases. Although pre-clinical studies have identified a number of manipulations that stimulate some degree of axon growth after CNS damage, the extent of recovery remains quite limited, emphasizing the need for improved therapies. Here, we used traumatic injury to the mouse optic nerve as a model system to test the effects of combining several treatments that have recently been found to promote axon regeneration without the risks associated with manipulating known tumor suppressors or oncogenes. The treatments tested here include TPEN, a chelator of mobile (free) zinc (Zn(2+)); shRNA against the axon growth-suppressing transcription factor Klf9; and the atypical growth factor oncomodulin combined with a cAMP analog. Whereas some combinatorial treatments produced only marginally stronger effects than the individual treatments alone, co-treatment with TPEN and Klf9 knockdown had a substantially stronger effect on axon regeneration than either one alone. This combination also promoted a high level of cell survival at longer time points. Thus, Zn(2+) chelation in combination with Klf9 suppression holds therapeutic potential for promoting axon regeneration after optic nerve injury, and may also be effective for treating other CNS injuries and diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Group in-course assessment promotes cooperative learning and increases performance.

    Science.gov (United States)

    Pratten, Margaret K; Merrick, Deborah; Burr, Steven A

    2014-01-01

    The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In-Course-Assessments (ICAs) to encourage teamwork. A student's final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two-way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P learning resources in an active, team-based, cooperative learning environment. © 2013 American Association of Anatomists.

  14. Structural basis of Ets1 cooperative binding to widely separated sites on promoter DNA.

    Directory of Open Access Journals (Sweden)

    Nigar D Babayeva

    Full Text Available Ets1 is a member of the Ets family of transcription factors. Ets1 is expressed in autoinhibited form and its DNA binding depends on partner proteins bound to adjacent sequences or the relative positioning of a second Ets-binding site (EBS. The autoinhibition of Ets1 is mediated by structural coupling of regions flanking the DNA-binding domain. The NMR structure of Ets1 revealed that the inhibitory regions comprised of helices HI1 and HI2 and H4 are packed together on the Ets domain to form an inhibitory module. The crystal structure of Ets1 unexpectedly revealed a homodimer in which homodimerisation occurs via swapping of HI1 helices. Modeling of DNA binding indicates that the Ets1 dimer can bind to two antiparallel pieces of DNA. To verify this, we crystallized and solved the structure of the complex comprised of Ets1 dimer and two pieces of DNA. DNA binding by Ets1 dimer resulted in formation of additional intermolecular protein•DNA interactions, implying that the complex formation is cooperative.

  15. Structural basis of Ets1 cooperative binding to widely separated sites on promoter DNA.

    Science.gov (United States)

    Babayeva, Nigar D; Baranovskaya, Oxana I; Tahirov, Tahir H

    2012-01-01

    Ets1 is a member of the Ets family of transcription factors. Ets1 is expressed in autoinhibited form and its DNA binding depends on partner proteins bound to adjacent sequences or the relative positioning of a second Ets-binding site (EBS). The autoinhibition of Ets1 is mediated by structural coupling of regions flanking the DNA-binding domain. The NMR structure of Ets1 revealed that the inhibitory regions comprised of helices HI1 and HI2 and H4 are packed together on the Ets domain to form an inhibitory module. The crystal structure of Ets1 unexpectedly revealed a homodimer in which homodimerisation occurs via swapping of HI1 helices. Modeling of DNA binding indicates that the Ets1 dimer can bind to two antiparallel pieces of DNA. To verify this, we crystallized and solved the structure of the complex comprised of Ets1 dimer and two pieces of DNA. DNA binding by Ets1 dimer resulted in formation of additional intermolecular protein•DNA interactions, implying that the complex formation is cooperative.

  16. Multilateral cooperation for literacy promotion under stress: governance and management issues

    Directory of Open Access Journals (Sweden)

    Leslie J. Limage

    2009-12-01

    Full Text Available This paper analyses recent organizational change and governance in UNESCO. The Organization has given priority to the promotion of universal literacy since its inception in 1946. It has persisted in its dual approach to universal literacy through both universal primary education and literacy learning opportunities through formal provision and non-formal learning opportunities for adults and out-of-school youth. A major policy shift in 2006 to abandon systematic and programmatic concern for literacy at UNESCO Headquarters drastically changed priorities. That decision is analysed in the broader UN system setting, United States’ policies since its return to UNESCO, and the recent internal governing dynamics of the agency.

  17. Viewpoint – The Role of the German Development Cooperation in Promoting Sustainable Hydropower

    Directory of Open Access Journals (Sweden)

    Cathleen Seeger

    2010-06-01

    Germany’s engagement in the promotion of participatory processes on dam-related issues is building on the WCD and follow-up processes, as outlined in this article. On the global level, BMZ, represented by the Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ, is currently part of the Hydropower Sustainability Assessment Forum (HSAF. On the national level, one example of support is the contribution to and interaction with the Ghana Dam Dialogue, which is facilitated through two local partners: the International Water Management Institute (IWMI and the Volta Basin Development Foundation (VBDF.

  18. PromoterCAD: Data-driven design of plant regulatory DNA.

    Science.gov (United States)

    Cox, Robert Sidney; Nishikata, Koro; Shimoyama, Sayoko; Yoshida, Yuko; Matsui, Minami; Makita, Yuko; Toyoda, Tetsuro

    2013-07-01

    Synthetic promoters can control the timing, location and amount of gene expression for any organism. PromoterCAD is a web application for designing synthetic promoters with altered transcriptional regulation. We use a data-first approach, using published high-throughput expression and motif data from for Arabidopsis thaliana to guide DNA design. We demonstrate data mining tools for finding motifs related to circadian oscillations and tissue-specific expression patterns. PromoterCAD is built on the LinkData open platform for data publication and rapid web application development, allowing new data to be easily added, and the source code modified to add new functionality. PromoterCAD URL: http://promotercad.org. LinkData URL: http://linkdata.org.

  19. Sustainable Carbon Dioxide Photoreduction by a Cooperative Effect of Reactor Design and Titania Metal Promotion

    Directory of Open Access Journals (Sweden)

    Alberto Olivo

    2018-01-01

    Full Text Available An effective process based on the photocatalytic reduction of CO2 to face on the one hand, the crucial problem of environmental pollution, and, on the other hand, to propose an efficient way to product clean and sustainable energy sources has been developed in this work. Particular attention has been paid to the sustainability of the process by using a green reductant (water and TiO2 as a photocatalyst under very mild operative conditions (room temperature and atmospheric pressure. It was shown that the efficiency in carbon dioxide photoreduction is strictly related to the process parameters and to the catalyst features. In order to formulate a versatile and high performing catalyst, TiO2 was modified by oxide or metal species. Copper (in the oxide CuO form or gold (as nanoparticles were employed as promoting metal. Both photocatalytic activity and selectivity displayed by CuO-TiO2 and Au-TiO2 were compared, and it was found that the nature of the promoter (either Au or CuO shifts the selectivity of the process towards two strategic products: CH4 or H2. The catalytic results were discussed in depth and correlated with the physicochemical features of the photocatalysts.

  20. Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF–TNF-RII binding in rheumatoid arthritis

    Science.gov (United States)

    2016-01-01

    The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3+ T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine. PMID:27270893

  1. The Cooperative Research Centre for Living with Autism (Autism CRC) Conceptual Model to Promote Mental Health for Adolescents with ASD.

    Science.gov (United States)

    Shochet, Ian M; Saggers, Beth R; Carrington, Suzanne B; Orr, Jayne A; Wurfl, Astrid M; Duncan, Bonnie M; Smith, Coral L

    2016-06-01

    Despite an increased risk of mental health problems in adolescents with autism spectrum disorder (ASD), there is limited research on effective prevention approaches for this population. Funded by the Cooperative Research Centre for Living with Autism, a theoretically and empirically supported school-based preventative model has been developed to alter the negative trajectory and promote wellbeing and positive mental health in adolescents with ASD. This conceptual paper provides the rationale, theoretical, empirical and methodological framework of a multilayered intervention targeting the school, parents and adolescents on the spectrum. Two important interrelated protective factors have been identified in community adolescent samples, namely the sense of belonging (connectedness) to school and the capacity for self and affect regulation in the face of stress (i.e. resilience). We describe how a confluence of theories from social psychology, developmental psychology and family systems theory, along with empirical evidence (including emerging neurobiological evidence), supports the interrelationships between these protective factors and many indices of wellbeing. However, the characteristics of ASD (including social and communication difficulties, and frequently difficulties with changes and transitions, and diminished optimism and self-esteem) impair access to these vital protective factors. The paper describes how evidence-based interventions at the school level for promoting inclusive schools (using the Index for Inclusion) and interventions for adolescents and parents to promote resilience and belonging [using the Resourceful Adolescent Program (RAP)] are adapted and integrated for adolescents with ASD. This multisite proof-of-concept study will confirm whether this multilevel school-based intervention is promising, feasible and sustainable.

  2. Identification of a positive regulatory element in the myelin-specific promoter of the PMP22 gene.

    Science.gov (United States)

    Hai, M; Bidichandani, S I; Patel, P I

    2001-09-15

    Over- and under expression of the 22 kDa peripheral myelin protein (PMP22) results in dysmyelinating peripheral neuropathies, such as Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy, with the liability to pressure palsies (HNPP). Expression of the PMP22 gene is driven by two alternative promoters, P1 and P2, with transcripts originating from P1 associated with peripheral nerve myelination by Schwann cells. Transient transfections of constructs containing P1 (3.5 kb) or P2 (2.5 kb) resulted in high levels of reporter gene expression in the RT4-D6P2T schwannoma cell line. Serial deletions of P1 revealed that region P1-A (-105 to -43), situated upstream of the minimal promoter, contained a positive regulatory element. The 62 bp P1-A region conferred in cis a sevenfold increase in expression of luciferase driven by a heterologous promoter in an orientation-dependent manner. Interspecies comparison of the P1-A region revealed a 98% degree of identity between the human, mouse, and rat sequences. A prominent sequence-dependent DNA-protein complex (C-I) was detected in electrophoretic mobility shift assays with P1-A using RT4-D6P2T nuclear extract and was localized to a minimal 21 bp region within P1-A. Site-directed mutagenesis of this region revealed nucleotides at positions -46 to -43 as being necessary for formation of C-I. Functional analysis of the mutated P1-A element indicated that positions -46 and -45 were essential for transactivation mediated by this element. Characterization of the transacting factor(s) interacting with this key regulatory element will shed light on its role in regulating peripheral nerve myelination. Copyright 2001 Wiley-Liss, Inc.

  3. REGULATORY INCENTIVES TO PROMOTE THE USE OF PHOTOVOLTAIC SYSTEMS IN BRAZIL

    Directory of Open Access Journals (Sweden)

    F. K. O. M. Varella

    2012-06-01

    Full Text Available The use of photovoltaic solar energy for electricity generation has been even more considered in many countries worldwide as an excellent alternative to reduce the man-made environmental impacts, especially those associated with climate changes. In countries such as Japan, Germany, USA and other European countries, specific regulatory mechanisms have been developed to stimulate its use either through governmental programs or financial and/or tax incentives. The main common reasons on these programs are the diversification of energy sources traditionally used, namely the need to adopt a sustainable energy model, the encouragement of the photovoltaic equipment industry, an affordable technology, and a concern with the environment, mainly to the reduction of CO2 emissions. In the Brazilian case, despite the large solar resource potential, many things still need to be done and, since then only a small number of initiatives were undertaken to encourage solar photovoltaic energy, but still very small when compared to the countries mentioned above. In this sense, this paper has the purpose of presenting the evolution of the regulatory incentives concerned to the use of photovoltaic solar energy in Brazil over the years.

  4. Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity

    Science.gov (United States)

    Raj, Prithvi; Rai, Ekta; Song, Ran; Khan, Shaheen; Wakeland, Benjamin E; Viswanathan, Kasthuribai; Arana, Carlos; Liang, Chaoying; Zhang, Bo; Dozmorov, Igor; Carr-Johnson, Ferdicia; Mitrovic, Mitja; Wiley, Graham B; Kelly, Jennifer A; Lauwerys, Bernard R; Olsen, Nancy J; Cotsapas, Chris; Garcia, Christine K; Wise, Carol A; Harley, John B; Nath, Swapan K; James, Judith A; Jacob, Chaim O; Tsao, Betty P; Pasare, Chandrashekhar; Karp, David R; Li, Quan Zhen; Gaffney, Patrick M; Wakeland, Edward K

    2016-01-01

    Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes. DOI: http://dx.doi.org/10.7554/eLife.12089.001 PMID:26880555

  5. Peyer's patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy.

    Directory of Open Access Journals (Sweden)

    Haruyo Nakajima-Adachi

    Full Text Available BACKGROUND AND OBJECTIVE: To improve the efficacy and safety of tolerance induction for food allergies, identifying the tissues responsible for inducing intestinal inflammation and subsequent oral tolerance is important. We used OVA23-3 mice, which express an ovalbumin-specific T-cell receptor, to elucidate the roles of local and systemic immune tissues in intestinal inflammation. METHODS AND RESULTS: OVA23-3 mice developed marked enteropathy after consuming a diet containing egg white (EW diet for 10 days but overcame the enteropathy (despite continued moderate inflammation after receiving EW diet for a total of 28 days. Injecting mice with anti-IL-4 antibody or cyclosporine A confirmed the involvement of Th2 cells in the development of the enteropathy. To assess the individual contributions of Peyer's patches (PPs, mesenteric lymph nodes (MLNs, and the spleen to the generation of effector CD4+ T-cells, we analyzed the IL-4 production, proliferation in response to ovalbumin, and CD4+ T-cell numbers of these tissues. EW feeding for 10 days induced significant IL-4 production in PPs, the infiltration of numerous CD4+ T-cells into MLNs, and a decrease in CD4+ T-cell numbers in spleen. On day 28, CD4+ T-cells from all tissues had attenuated responses to ovalbumin, suggesting tolerance acquisition, although MLN CD4+ T-cells still maintained IL-4 production with proliferation. In addition, removal of MLNs but not the spleen decreased the severity of enteropathy and PP-disrupted mice showed delayed onset of EW-induced inflammatory responses. Disruption of peripheral lymphoid tissues or of both PPs and MLNs almost completely prevented the enteropathy. CONCLUSIONS: PPs and MLNs coordinately promote enteropathy by generating effector T-cells during the initial and exacerbated phases, respectively; the spleen is dispensable for enteropathy and shows tolerogenic responses throughout EW-feeding. The regulation of PPs may suppress the initiation of

  6. P2Y2 Receptor and EGFR Cooperate to Promote Prostate Cancer Cell Invasion via ERK1/2 Pathway.

    Directory of Open Access Journals (Sweden)

    Wei-Hua Li

    Full Text Available As one member of G protein-coupled P2Y receptors, P2Y2 receptor can be equally activated by extracellular ATP and UTP. Our previous studies have proved that activation of P2Y2 receptor by extracellular ATP could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1, and the most significant change in expression of IL-8 was observed after P2Y2 receptor activation. However, the signaling pathway downstream of P2Y2 receptor and the role of IL-8 in P2Y2-mediated prostate cancer cell invasion remain unclear. Here, we found that extracellular ATP/UTP induced activation of EGFR and ERK1/2. After knockdown of P2Y2 receptor, the ATP -stimulated phosphorylation of EGFR and ERK1/2 was significantly suppressed. Further experiments showed that inactivation of EGFR and ERK1/2 attenuated ATP-induced invasion and migration, and suppressed ATP-mediated IL-8 production. In addition, knockdown of IL-8 inhibited ATP-mediated invasion and migration of prostate cancer cells. These findings suggest that P2Y2 receptor and EGFR cooperate to upregulate IL-8 production via ERK1/2 pathway, thereby promoting prostate cancer cell invasion and migration. Thus blocking of the P2Y2-EGFR-ERK1/2 pathway may provide effective therapeutic interventions for prostate cancer.

  7. MYB Promotes Desmoplasia in Pancreatic Cancer through Direct Transcriptional Up-regulation and Cooperative Action of Sonic Hedgehog and Adrenomedullin.

    Science.gov (United States)

    Bhardwaj, Arun; Srivastava, Sanjeev K; Singh, Seema; Tyagi, Nikhil; Arora, Sumit; Carter, James E; Khushman, Moh'd; Singh, Ajay P

    2016-07-29

    Extensive desmoplasia is a prominent pathological characteristic of pancreatic cancer (PC) that not only impacts tumor development, but therapeutic outcome as well. Recently, we demonstrated a novel role of MYB, an oncogenic transcription factor, in PC growth and metastasis. Here we studied its effect on pancreatic tumor histopathology and associated molecular and biological mechanisms. Tumor-xenografts derived from orthotopic-inoculation of MYB-overexpressing PC cells exhibited far-greater desmoplasia in histological analyses compared with those derived from MYB-silenced PC cells. These findings were further confirmed by immunostaining of tumor-xenograft sections with collagen-I, fibronectin (major extracellular-matrix proteins), and α-SMA (well-characterized marker of myofibroblasts or activated pancreatic stellate cells (PSCs)). Likewise, MYB-overexpressing PC cells provided significantly greater growth benefit to PSCs in a co-culture system as compared with the MYB-silenced cells. Interrogation of deep-sequencing data from MYB-overexpressing versus -silenced PC cells identified Sonic-hedgehog (SHH) and Adrenomedullin (ADM) as two differentially-expressed genes among others, which encode for secretory ligands involved in tumor-stromal cross-talk. In-silico analyses predicted putative MYB-binding sites in SHH and ADM promoters, which was later confirmed by chromatin-immunoprecipitation. A cooperative role of SHH and ADM in growth promotion of PSCs was confirmed in co-culture by using their specific-inhibitors and exogenous recombinant-proteins. Importantly, while SHH acted exclusively in a paracrine fashion on PSCs and influenced the growth of PC cells only indirectly, ADM could directly impact the growth of both PC cells and PSCs. In summary, we identified MYB as novel regulator of pancreatic tumor desmoplasia, which is suggestive of its diverse roles in PC pathobiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intra-muscular fat content

    LENUS (Irish Health Repository)

    Aslan, Ozlem

    2010-12-15

    Abstract Background Recent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures. Results Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed) as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs) and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P < 0.05). While no single SNP was associated with intramuscular fat (IMF), a clear association with increased IMF and juiciness was observed for haplotype 2. Conclusion The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF\\/juiciness or tenderness in a genome-assisted selection framework.

  9. Report on the fiscal 1996 research cooperation promotion project, `the research cooperation diagnosis survey`; 1996 nendo kenkyu kyoryoku jigyo `kenkyu kyoryoku shindan chosa` hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    A diagnosis survey was conducted for Japan to cooperate in researching subjects on technical development in developing countries. In fiscal 1996, surveys were made on the following: (1) establishment of the industrial base (Vietnam), (2) preservation of biological diversification and the continuous utilization (Brazil), (3) fostering of the industry of automobile parts (Thailand), (4) finding out of items on environment related fields (India), (5) environmental response type system for effective use of water resource (the Philippines), (6) small size geothermal exploration in remote islands (Indonesia). (1) is research cooperation for welding technology, powder metallurgy technology, hypoid gear manufacturing technology, and iron making technology by the direct reduction method. In (2), research/development are conducted in cooperation with research institutes in Brazil on survey/identification/utilization of bioactive substances from biological resources in Brazil. In (4), an examination was made of the seeds for research cooperation in technical fields such as environment and energy. Having a strong relation with the industrial circle, SCIR is carrying out researches on aerospace, petrochemical, biology, electronics, medicines/drug, etc., which indicated fulfillment of intellectual infrastructure in India. 52 figs.

  10. Repetitive pertussis toxin promotes development of regulatory T cells and prevents central nervous system autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Martin S Weber

    2010-12-01

    Full Text Available Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS. Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE can be enhanced by concomitant administration of pertussis toxin (PTx, the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS. In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4(+CD25(+FoxP3(+ regulatory T cells (Treg. Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4(+CD25(+FoxP3(+ Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation.

  11. CD4+IL-21+T cells are correlated with regulatory T cells and IL-21 promotes regulatory T cells survival during HIV infection.

    Science.gov (United States)

    Zhang, Zi-Ning; Bai, Li-Xin; Fu, Ya-Jing; Jiang, Yong-Jun; Shang, Hong

    2017-03-01

    IL-21 enhances T and natural killer cells survival and antiviral functions without promoting T cell activation during HIV infection, which makes it a better adjuvant in anti-HIV immunotherapy. Due to the pleiotropy and redundancy of cytokines, it is vital to have a comprehensive knowledge of the role of IL-21 in the regulation of immune responses. Regulatory T cells (Tregs) play an important role in immune regulation and are a determinant of immune therapeutic efficacy in certain circumstances. In this study, we explored the direct effect of IL-21 on Tregs during HIV infection, which has not been addressed before. Thirty-four HIV treatment-naïve patients were enrolled and the relationship between CD4 + IL-21 + T cells and Tregs were studied. The effects of IL-21 on CD4 + CD25 + CD127 low Tregs' apoptosis, proliferation, and CTLA-4 and TGF-β expression in HIV-infected patients was investigated and compared with the effect of other common γ-chain cytokines. We found the percentage and absolute numbers of CD4 + IL-21 + T cells were positively related to the frequency or absolute numbers of CD4 + CD25 + or CD4 + CD25 + CD127 low Tregs. Compared with the media-alone control, IL-21, IL-7, and IL-15 could significantly reduce apoptosis of Tregs (pHIV infected patients. There were no significant differences of the fold induction of apoptosis, proliferation, or CTLA-4 and TGF-β expression by Tregs from HIV-infected patients and normal controls after IL-21 treatment. In vitro experiment showed that pretreatment with IL-21 significantly enhanced the suppressive effect of Tregs on CD8+ T cells' IFN-γ expression. We conclude that IL-21 promotes the survival and CTLA-4 expression of Tregs and enhanced the suppressive capacity of Tregs during HIV infection. These results broaden the understanding of HIV pathogenesis and provide critical information for HIV interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Gynura procumbens Ethanolic Extract Promotes Lymphocyte Activation and Regulatory T Cell Generation In Vitro

    Directory of Open Access Journals (Sweden)

    Dinia Rizqi Dwijayanti

    2015-01-01

    Full Text Available Immune system is a system of biological structures and processes within organism directed to protect against invaded pathogen. Cellular and humoral immune system mediated by immunocompetent cells such as CD4+ T cells, CD8+ T cells, CD4+ CD25+ T cells, and B220 cells play important role for maintaining immunological surveillance. The purpose of this study was to determine the effect of ethanolic extract of G. procumbens leaves (EEGL on the profile of CD4+ T cells, CD4+ CD25+ T cells, and B220+ cells. Splenic cells were isolated from BALB/c mice and cultured in RPMI1640 medium in the presence of EEGL. After 4 days of incubation, cells were harvested, stained with antibodies and analyzed by flow cytometer. The data were analyzed by one-way ANOVA with α= 0.05 and Tukey test using SPSS 16.0 for windows. The results showed that the extract of G. procumbens could increase proliferation of CD4+ CD62L- T cell, CD4+ CD25+ T cells, and B220+ cells compared to the control. Here, we showed the biological effect of G. procumbens as medicinal herb with immunomodulatory activity and the dose of 0.1 μg/ml and 1.0 μg/ml could promote T cell activation compared to the highest dose of 10 μg/ml. Interestingly, the dose of 10 μg/ml rather promote than inhibit B cell proliferation.

  13. TpF1 from Treponema pallidum activates inflammasome and promotes the development of regulatory T cells.

    Science.gov (United States)

    Babolin, Chiara; Amedei, Amedeo; Ozolins, Dzintars; Zilevica, Aija; D'Elios, Mario Milco; de Bernard, Marina

    2011-08-01

    Human syphilis is a multistage disease, with diverse and wide-ranging manifestations caused by Treponema pallidum. Despite the fact that a cell-mediated immune response takes part in the course of syphilis, T. pallidum often manages to evade host immunity and, in untreated individuals, may trigger chronic infection. With this study, we demonstrate for the first time, to our knowledge, that Treponema pallidum induces a regulatory T (Treg) response in patients with secondary syphilis and we found that the miniferritin TpF1, produced by the bacterium, is able to expand this response and promote the production of TGF-β. Accordingly, TpF1 stimulates monocytes to release IL-10 and TGF-β, the key cytokines in driving Treg cell differentiation. Interestingly, we also found that TpF1 stimulates monocytes to synthesize and release several proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, the latter following the activation of the multiprotein complex inflammasome. Collectively, these data strongly support a central role for TpF1 both in the inflammation process, which occurs in particular during the early stage of syphilis, and in the long-term persistence of the spirochete within the host by promoting Treg response and TGF-β production.

  14. Biorepository regulatory frameworks: building parallel resources that both promote scientific investigation and protect human subjects.

    Science.gov (United States)

    Marko-Varga, György; Baker, Mark S; Boja, Emily S; Rodriguez, Henry; Fehniger, Thomas E

    2014-12-05

    the future. In this brief overview, we provide practical information to the potential users of biorepositories about some of the current developments in both the methodology of sample acquisition and in the regulatory environment governing their use.

  15. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  16. Decidual vascular endothelial cells promote maternal-fetal immune tolerance by inducing regulatory T cells through canonical Notch1 signaling.

    Science.gov (United States)

    Yao, Yanyi; Song, Jieping; Wang, Weipeng; Liu, Nian

    2016-05-01

    Adaptation of the maternal immune response to accommodate the semiallogeneic fetus is necessary for pregnancy success. However, the mechanisms by which the fetus avoids rejection despite expression of paternal alloantigens remain incompletely understood. Regulatory T cells (Treg cells) are pivotal for maintaining immune homeostasis, preventing autoimmune disease and fetus rejection. In this study, we found that maternal decidual vascular endothelial cells (DVECs) sustained Foxp3 expression in resting Treg cells in vitro. Moreover, under in vitro Treg cell induction condition with agonistic antibodies and transforming growth factor (TGF)-β, DVECs promoted Treg cell differentiation from non-Treg conventional T cells. Consistent with the promotion of Treg cell maintenance and differentiation, Treg cell-associated gene expression such as TGF-β, Epstein-Barr-induced gene-3, CD39 and glucocorticoid-induced tumor necrosis factor receptor was also increased in the presence of DVECs. Further study revealed that DVECs expressed Notch ligands such as Jagged-1, Delta-like protein 1 (DLL-1) and DLL-4, while Treg cells expressed Notch1 on their surface. The effects of DVECs on Treg cells was inhibited by siRNA-induced knockdown of expression of Jagged-1 and DLL-1 in DVECs. Downregulation of Notch1 in Treg cells using lentiviral shRNA transduction decreased Foxp3 expression in Treg cells. Adoptive transfer of Notch1-deficient Treg cells increased abortion rate in a murine semiallogeneic pregnancy model. Taken together, our study suggests that maternal DVECs are able to maintain decidual Treg cell identity and promote Treg cell differentiation through activation of Notch1 signal pathway in Treg cells and subsequently inhibit the immune response against semiallogeneic fetuses and preventing spontaneous abortion.

  17. Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.

    Science.gov (United States)

    Diaz, Miguel F; Vaidya, Abishek B; Evans, Siobahn M; Lee, Hyun J; Aertker, Benjamin M; Alexander, Alexander J; Price, Katherine M; Ozuna, Joyce A; Liao, George P; Aroom, Kevin R; Xue, Hasen; Gu, Liang; Omichi, Rui; Bedi, Supinder; Olson, Scott D; Cox, Charles S; Wenzel, Pamela L

    2017-05-01

    Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E 2 (PGE 2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement. Stem Cells 2017;35:1259-1272. © 2017 AlphaMed Press.

  18. Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science.

    Science.gov (United States)

    Mushak, Paul; Elliott, Kevin C

    2015-12-01

    The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field. It focuses on hormesis, described as a type of dose-response relationship in toxicology and biology showing low-dose stimulation but high-dose inhibition, or the reverse. Hormesis proponents tout its significance, arguing that substances toxic at high doses and beneficial at lower doses should be regulated less stringently. We identify five strategies employed by hormesis proponents to foster its acceptance: (1) creating institutions focused on supporting hormesis; (2) developing terminology, study designs, and data interpretations that cast it in a favorable light; (3) using bibliometric techniques and surveys to attract attention; (4) aggressively advocating for the phenomenon and challenging critics; and (5) working with outside interest groups to apply the hormesis phenomenon in the economic and political spheres. We also suggest a number of oversight strategies that can be implemented to help promote credible and socially responsible research in cases like this one.

  19. Report on the fiscal 1995 research cooperation promotion project, `the research cooperation diagnosis survey`; 1995 nendo kenkyu kyoryoku suishin jigyo `kenkyu kyoryoku shindan chosa` hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    A diagnosis survey was conducted for Japan to cooperate in researching subjects on technical development in developing countries. In fiscal 1995, surveys were made on the following: (1) recycling technology of biomass industrial waste in the tropical region, (2) small size geothermal exploration in remote islands, (3) waste water recycling system using activated carbon, etc., (4) upgrading of proofreading technology of measuring standards, (5) technology to simply set up conditions for forming engineering plastics, (6) assessment of safety of chemical substances. In (1), energy and useful matters are recovered from oil palm of Indonesia by thermal decomposition technology. In (2), a system is constructed which can effectively explore geothermal energy in remote islands in the east Indonesia. As to (3), a survey is conducted in the Philippines. (4) contributes to upgrading of length measuring standards in Thailand. (5) attempts to improve technology of forming engineering plastics. In (6), research cooperation is made for preventing environmental pollution and health damage by chemical substances from happening in Thailand and for technology for assessing safety of chemical substances which contributes to the proper use of the hazardous material law in Thailand. 28 figs.

  20. Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

    Science.gov (United States)

    Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

    2002-11-01

    We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells.

  1. Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression.

    Science.gov (United States)

    Kondo, Ayano; Yamamoto, Shogo; Nakaki, Ryo; Shimamura, Teppei; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Yoshida, Tetsuo; Aburatani, Hiroyuki; Osawa, Tsuyoshi

    2017-02-28

    Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Retinoic acid and rapamycin differentially affect and synergistically promote the ex vivo expansion of natural human T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Tatiana N Golovina

    Full Text Available Natural T regulatory cells (Tregs are challenging to expand ex vivo, and this has severely hindered in vivo evaluation of their therapeutic potential. All trans retinoic acid (ATRA plays an important role in mediating immune homeostasis in vivo, and we investigated whether ATRA could be used to promote the ex vivo expansion of Tregs purified from adult human peripheral blood. We found that ATRA helped maintain FOXP3 expression during the expansion process, but this effect was transient and serum-dependent. Furthermore, natural Tregs treated with rapamycin, but not with ATRA, suppressed cytokine production in co-cultured effector T cells. This suppressive activity correlated with the ability of expanded Tregs to induce FOXP3 expression in non-Treg cell populations. Examination of CD45RA+ and CD45RA- Treg subsets revealed that ATRA failed to maintain suppressive activity in either population, but interestingly, Tregs expanded in the presence of both rapamycin and ATRA displayed more suppressive activity and had a more favorable epigenetic status of the FOXP3 gene than Tregs expanded in the presence of rapamycin only. We conclude that while the use of ATRA as a single agent to expand Tregs for human therapy is not warranted, its use in combination with rapamycin may have benefit.

  3. Promoting prosocial behavior and self-regulatory skills in preschool children through a mindfulness-based Kindness Curriculum.

    Science.gov (United States)

    Flook, Lisa; Goldberg, Simon B; Pinger, Laura; Davidson, Richard J

    2015-01-01

    Self-regulatory abilities are robust predictors of important outcomes across the life span, yet they are rarely taught explicitly in school. Using a randomized controlled design, the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum (KC) delivered in a public school setting on executive function, self-regulation, and prosocial behavior in a sample of 68 preschool children. The KC intervention group showed greater improvements in social competence and earned higher report card grades in domains of learning, health, and social-emotional development, whereas the control group exhibited more selfish behavior over time. Interpretation of effect sizes overall indicate small to medium effects favoring the KC group on measures of cognitive flexibility and delay of gratification. Baseline functioning was found to moderate treatment effects with KC children initially lower in social competence and executive functioning demonstrating larger gains in social competence relative to the control group. These findings, observed over a relatively short intervention period, support the promise of this program for promoting self-regulation and prosocial behavior in young children. They also support the need for future investigation of program implementation across diverse settings.

  4. Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3.

    Science.gov (United States)

    de la Garza, Gabriel; Schleiffarth, Jack Robert; Dunnwald, Martine; Mankad, Anuj; Weirather, Jason L; Bonde, Gregory; Butcher, Stephen; Mansour, Tamer A; Kousa, Youssef A; Fukazawa, Cindy F; Houston, Douglas W; Manak, J Robert; Schutte, Brian C; Wagner, Daniel S; Cornell, Robert A

    2013-01-01

    IFN regulatory factor 6 (IRF6) is a transcription factor that, in mammals, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the transcriptional targets that mediate these effects are currently unknown. In zebrafish and frog embryos, Irf6 is necessary for differentiation of the embryonic superficial epithelium, or periderm. Here we use microarrays to identify genes that are expressed in the zebrafish periderm and whose expression is inhibited by a dominant-negative variant of Irf6 (dnIrf6). These methods identify Grainyhead-like 3 (Grhl3), an ancient regulator of the epidermal permeability barrier, as acting downstream of Irf6. In human keratinocytes, IRF6 binds conserved elements near the GRHL3 [corrected] promoter. We show that one of these elements has enhancer activity in human keratinocytes and zebrafish periderm, suggesting that Irf6 directly stimulates Grhl3 expression in these tissues. Simultaneous inhibition of grhl1 and grhl3 disrupts periderm differentiation in zebrafish, and, intriguingly, forced grhl3 expression restores periderm markers in both zebrafish injected with dnIrf6 and frog embryos depleted of Irf6. Finally, in Irf6-deficient mouse embryos, Grhl3 expression in the periderm and oral epithelium is virtually absent. These results indicate that Grhl3 is a key effector of Irf6 in periderm differentiation.

  5. Comparative promoter analysis of doxorubicin resistance-associated genes suggests E47 as a key regulatory element.

    Science.gov (United States)

    Gyorffy, András; Vásárhelyi, Barna; Szöke, Dominika; Dietel, Manfred; Tulassay, Tivadar; Györffy, Balázs

    2006-01-01

    Working under the assumption that up- or downregulation of genes implicated in chemoresistance may be the result of altered function of regulatory transcription factors (TF), over-represented TF-binding sites of gene lists previously associated with doxorubicin resistance were the target of our search. First, a data warehouse was set up containing 52 genes which were present in at least two gene lists; of those, proximal promoter sequences (1 kb upstream and 0.05 kb downstream of the transcriptional start sites) could be retrieved from genomic databases for 45 genes using the EZ-Retrieve. The TOUCAN tool MotifScanner, which searches the TRANSFAC database, was used to detect TF-binding sites (TFBSs) in our set of sequences. The statistics tool of the Java program TOUCAN was applied to the data with the appropriate expected frequencies file to compare the measured prevalence to a background model. The most significantly over-represented TFBS was that of E47 (p=0.00024, prevalence: 0.2 vs. background: 8.19E-6). In summary, based on the results of our analysis it is hypothesized that the E47 transcription factor may contribute to doxorubicin resistance.

  6. Status of nuclear regulatory research and its future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. I.; Kim, W. S.; Kim, M. W. [KINS, Taejon (Korea, Republic of)

    1999-10-01

    A comprehensive investigation of the regulatory research comprising an examination of the research system, its areas and contents, and the goals and financial resources is undertaken. As a result of this study, the future direction of regulatory research and its implementation strategies are suggested to resolve the current issues emerging from this examination. The major issues identified in the study are; (a) an insufficient investment in nuclear regulatory and safety research, (b) an interfacial discrepancy between similar research areas, and (c) a limitation of utilizing research results. To resolve these issues, several measures are proposed : (1) developing a lead project to establish a comprehensive infrastructure for enhancing research cooperation between nuclear organizations including institutes, industry, and universities, with an aim to improve cooperation between projects and to strengthen overall coordination functions among research projects, (2) introducing a certification system on research outcome to promote the proliferation of both research results themselves and their application with a view to enhancing the research quality, (3) strengthening the cooperative system to promote the international cooperative research, and (4) digitalizing all documents and materials relevant to safety and regulatory research to establish KIMS (knowledge and information based management system). It is expected that the aforementioned measures suggested in this study will enhance the efficiency and effectiveness of both nuclear regulatory and safety research, if they are implemented after deliberating with the government and related nuclear industries in the near future.

  7. A simple promoter containing two Sp1 sites controls the expression of sterol-regulatory-element-binding protein 1a (SREBP-1a)

    OpenAIRE

    Zhang, Chengkang; Shin, Dong-Ju; Osborne, Timothy F.

    2005-01-01

    The mammalian gene for SREBP-1 (sterol-regulatory-element-binding protein 1) contains two promoters that control the production of two proteins, SREBP-1a and -1c, and each contains a unique N-terminal transcriptional activation domain, but they are otherwise identical. The relative level of each mRNA varies from tissue to tissue and they respond differently to regulatory stimuli. SREBP-1c is more abundantly expressed in liver, where its level is also regulated by insulin and liver X receptor ...

  8. From Scorecard to Social Learning: A Reflective Coassessment Approach for Promoting Multiagency Cooperation in Natural Resource Management

    Directory of Open Access Journals (Sweden)

    Dirk J. Roux

    2011-03-01

    Full Text Available The responsibility for managing and conserving freshwater ecosystems is typically shared by multiple organizations with sometimes conflicting policy mandates. However, scorecard-based approaches for measuring management effectiveness in natural resource management are usually confined to single organizations. This paper describes a social learning approach which acknowledges cooperation as an essential precondition for effective management and that encourages reflective coassessment of cooperative relationships. The approach was pilot tested with eight participating organizations in one water management area in South Africa. It specifically aimed to allow for a multiagency reflective assessment of issues determining cooperative behavior, allow context-specific adaptations, and be embedded in adaptive management. It involved development of a spreadsheet-based scorecard-type tool that can be used to facilitate a multiagency workshop. This workshop serves to bring parties face-to-face and helps them codiscover their interdependence, shortcomings, and strengths. The spreadsheet structures reflection on their respective roles and effectiveness while the reflective coassessment motivates participants to address shortcomings. Overall, insights that emerged included: cooperation should be an explicit component of each organization's operational strategy; facilitation of appropriate cooperative behavior could be very effectively achieved by external "bridging organizations"; the reflective assessment process must be followed by purposefully adaptive interventions; the ability of the scorecard to be contextually adaptive was important; and institutional readiness requires investigation as the approach does sit somewhat uncomfortably with much current practice.

  9. Allies Advancing Justice: Cooperation between U.S. Bishops and Call to Action to Promote the Peace and Economic Pastoral Letters (1982–1987

    Directory of Open Access Journals (Sweden)

    Anthony J. Pogorelc

    2012-10-01

    Full Text Available This article discusses a phase of an ongoing relationship between a social movement organization (SMO, Call to Action, and the institutional organization (IO in which it is embedded, the Catholic Church. Relationships between SMOs and IOs are dynamic. At times they may engage in heated conflict related to the SMO’s goal to reform the IO and the desire of the IO leaders to maintain stability. There can also be times when such relationships are less adversarial and even cooperative. This article draws on periodicals, archival data and interviews to describe and analyze a period (1982–1987 when the values and interests of Call to Action and U.S. Bishops coalesced and led to a period of cooperation in which they together promoted the Peace and Economic Pastoral Letters written by the U.S. Conference of Bishops.

  10. Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens.

    Science.gov (United States)

    Niu, Jun; Wang, Jia; Hu, Huiwen; Chen, Yinlei; An, Jiyong; Cai, Jian; Sun, Runze; Sheng, Zhongting; Liu, Xieping; Lin, Shanzhi

    2016-02-08

    MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5' deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process.

  11. How Can Managers Promote Salespeople's Person-Job Fit? The Effects of Cooperative Learning and Perceived Organizational Support

    Science.gov (United States)

    Tseng, Lu-Ming; Yu, Tsu-Wei

    2016-01-01

    Purpose: This paper aims to examine the impact of salespeople's subjective person-job fit on the salespeople's intention to quit. Moreover, this study further investigates how the subjective person -job fit could be influenced by the cooperative learning and support in the organization. Person-job fit is an important issue for salespeople's career…

  12. A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression.

    Science.gov (United States)

    Fang, Ziyu; Xu, Chen; Li, Yaoming; Cai, Xiaobing; Ren, Shancheng; Liu, Houqi; Wang, Yue; Wang, Fubo; Chen, Rui; Qu, Min; Wang, Yang; Zhu, Yasheng; Zhang, Wei; Shi, Xiaolei; Yao, Jingjing; Gao, Xu; Hou, Jianguo; Xu, Chuanliang; Sun, Yinghao

    2016-04-28

    We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  14. Cooperative contributions of Interferon regulatory factor 1 (IRF1 and IRF8 to interferon-γ-mediated cytotoxic effects on oligodendroglial progenitor cells

    Directory of Open Access Journals (Sweden)

    Pleasure David

    2011-01-01

    Full Text Available Abstract Background Administration of exogenous interferon-γ (IFNγ aggravates the symptoms of multiple sclerosis (MS, whereas interferon-β (IFNβ is used for treatment of MS patients. We previously demonstrated that IFNγ induces apoptosis of oligodendroglial progenitor cells (OPCs, suggesting that IFNγ is more toxic to OPCs than IFNβ. Thus we hypothesized that a difference in expression profiles between IFNγ-inducible and IFNβ-inducible genes in OPCs would predict the genes responsible for IFNγ-mediated cytotoxic effects on OPCs. We have tested this hypothesis particularly focusing on the interferon regulatory factors (IRFs well-known transcription factors up-regulated by IFNs. Methods Highly pure primary rat OPC cultures were treated with IFNγ and IFNβ. Cell death and proliferation were assessed by MTT reduction, caspse-3-like proteinase activity, Annexin-V binding, mitochondrial membrane potential, and BrdU-incorporation. Induction of all nine IRFs was comprehensively compared by quantitative PCR between IFNγ-treated and IFNβ-treated OPCs. IRFs more strongly induced by IFNγ than by IFNβ were selected, and tested for their ability to induce OPC apoptosis by overexpression and by inhibition by dominant-negative proteins or small interference RNA either in the presence or absence of IFNγ. Results Unlike IFNγ, IFNβ did not induce apoptosis of OPCs. Among nine IRFs, IRF1 and IRF8 were preferentially up-regulated by IFNγ. In contrast, IRF7 was more robustly induced by IFNβ than by IFNγ. Overexpressed IRF1 elicited apoptosis of OPCs, and a dominant negative IRF1 protein partially protected OPCs from IFNγ-induced apoptosis, indicating a substantial contribution of IRF1 to IFNγ-induced OPC apoptosis. On the other hand, overexpression of IRF8 itself had only marginal proapoptotic effects. However, overexpressed IRF8 enhanced the IFNγ-induced cytotoxicity and the proapoptotic effect of overexpressed IRF1, and down-regulation of

  15. Promoter analysis reveals cis-regulatory motifs associated with the expression of the WRKY transcription factor CrWRKY1 in Catharanthus roseus.

    Science.gov (United States)

    Yang, Zhirong; Patra, Barunava; Li, Runzhi; Pattanaik, Sitakanta; Yuan, Ling

    2013-12-01

    WRKY transcription factors (TFs) are emerging as an important group of regulators of plant secondary metabolism. However, the cis-regulatory elements associated with their regulation have not been well characterized. We have previously demonstrated that CrWRKY1, a member of subgroup III of the WRKY TF family, regulates biosynthesis of terpenoid indole alkaloids in the ornamental and medicinal plant, Catharanthus roseus. Here, we report the isolation and functional characterization of the CrWRKY1 promoter. In silico analysis of the promoter sequence reveals the presence of several potential TF binding motifs, indicating the involvement of additional TFs in the regulation of the TIA pathway. The CrWRKY1 promoter can drive the expression of a β-glucuronidase (GUS) reporter gene in native (C. roseus protoplasts and transgenic hairy roots) and heterologous (transgenic tobacco seedlings) systems. Analysis of 5'- or 3'-end deletions indicates that the sequence located between positions -140 to -93 bp and -3 to +113 bp, relative to the transcription start site, is critical for promoter activity. Mutation analysis shows that two overlapping as-1 elements and a CT-rich motif contribute significantly to promoter activity. The CrWRKY1 promoter is induced in response to methyl jasmonate (MJ) treatment and the promoter region between -230 and -93 bp contains a putative MJ-responsive element. The CrWRKY1 promoter can potentially be used as a tool to isolate novel TFs involved in the regulation of the TIA pathway.

  16. The Austrian Approach in Promoting Partnership in Balkan Areas: Research Cooperation and Networking between Austria, Kosovo and South Eastern Europe

    OpenAIRE

    SALIH S.

    2009-01-01

    Creating and improving the partnerships in order to strengthen the cooperation between institutions andcontribute towards a sustainable regional scientific collaboration is of major preoccupation for the Austrian Science andBalkan areas. Permanent work in maintaining a diversity of wheat plants and cultivars is a key to survival of plants,which are undergone to the new abiotic and biotic stress (climatic condition, pests and disease) demonstrates to be asuitable issue to ve approached in this...

  17. KLF6 cooperates with NUR77 and SF1 to activate the human INSL3 promoter in mouse MA-10 leydig cells.

    Science.gov (United States)

    Tremblay, Maxime A; Mendoza-Villarroel, Raifish E; Robert, Nicholas M; Bergeron, Francis; Tremblay, Jacques J

    2016-04-01

    Insulin-like 3 (INSL3), a Leydig cell-specific hormone, is essential for testis descent during foetal life and bone metabolism in adults. Despite its essential roles in male reproductive and bone health, very little is known regarding its transcriptional regulation in Leydig cells. To date, few transcription factors have been shown to activate INSL3 promoter activity: the nuclear receptors AR, NUR77, COUP-TFII and SF1. To identify additional regulators, we have isolated and performed a detailed analysis of a 1.1 kb human INSL3 promoter fragment. Through 5' progressive deletions and site-directed mutagenesis, we have mapped a 10 bp element responsible for about 80% of INSL3 promoter activity in Leydig cells. This element is identical to the CPE element of the placental-specific glycoprotein-5 (PSG5) promoter that is recognized by the developmental regulator Krüppel-like factor 6 (KLF6). Using PCR and western blotting, we found that KLF6 is expressed in several Leydig and Sertoli cell lines. Furthermore, immunohistochemistry on adult mouse testis revealed the presence of KLF6 in the nuclei of both Leydig and Sertoli cells. KLF6 binds to the 10 bp KLF element at -108 bp and activates the -1.1 kb human, but not the mouse, INSL3 promoter. KLF6-mediated activation of the human INSL3 promoter required an intact KLF element as well as Leydig/Sertoli-enriched factors because KLF6 did not stimulate the human INSL3 promoter activity in CV-1 fibroblast cells. Consistent with this, we found that KLF6 transcriptionally cooperates with NUR77 and SF1. Collectively, our results identify KLF6 as a regulator of human INSL3 transcription. © 2016 Society for Endocrinology.

  18. K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder

    Directory of Open Access Journals (Sweden)

    Imran Ahmad

    2011-07-01

    The human fibroblast growth factor receptor 3 (FGFR3 gene is frequently mutated in superficial urothelial cell carcinoma (UCC. To test the functional significance of FGFR3 activating mutations as a ‘driver’ of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1 activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer.

  19. K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder.

    Science.gov (United States)

    Ahmad, Imran; Singh, Lukram Babloo; Foth, Mona; Morris, Carol-Ann; Taketo, Makoto Mark; Wu, Xue-Ru; Leung, Hing Y; Sansom, Owen J; Iwata, Tomoko

    2011-07-01

    The human fibroblast growth factor receptor 3 (FGFR3) gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 activating mutations as a 'driver' of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1) activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer.

  20. Rice Phytochrome-Interacting Factor-Like1 (OsPIL1) is involved in the promotion of chlorophyll biosynthesis through feed-forward regulatory loops.

    Science.gov (United States)

    Sakuraba, Yasuhito; Kim, Eun-Young; Han, Su-Hyun; Piao, Weilan; An, Gynheung; Todaka, Daisuke; Yamaguchi-Shinozaki, Kazuko; Paek, Nam-Chon

    2017-07-10

    In phototrophic plants, the highly conserved and tightly regulated process of chlorophyll (Chl) biosynthesis comprises multi-step reactions involving more than 15 enzymes. Since the efficiency of Chl biosynthesis strongly affects plant productivity, understanding the underlying regulatory mechanisms in crop plants can be useful for strategies to increase grain and biomass yields. Here, we show that rice (Oryza sativa) Phytochrome-Interacting Factor-Like1 (OsPIL1), a basic helix-loop-helix transcription factor, promotes Chl biosynthesis. The T-DNA insertion knockdown ospil1 mutant showed a pale-green phenotype when grown in a natural paddy field. Transcriptome analysis revealed that several genes responsible for Chl biosynthesis and photosynthesis were significantly down-regulated in ospil1 leaves. Using promoter binding and transactivation assays, we found that OsPIL1 binds to the promoters of two Chl biosynthetic genes, OsPORB and OsCAO1, and promotes their transcription. In addition, OsPIL1 directly up-regulates the expression of two transcription factor genes, GOLDEN2-LIKE1 (OsGLK1) and OsGLK2. OsGLK1 and OsGLK2 both bind to the promoters of OsPORB and OsCAO1, as well as some of genes encoding the light-harvesting complex of photosystems, probably promoting their transcription. Thus, OsPIL1 is involved in the promotion of Chl biosynthesis by up-regulating the transcription of OsPORB and OsCAO1 via trifurcate feed-forward regulatory loops involving two OsGLKs. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.

    Science.gov (United States)

    Noval Rivas, Magali; Burton, Oliver T; Oettgen, Hans C; Chatila, Talal

    2016-09-01

    Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. We sought to investigate the role of ILC2s in food allergy. Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. The in vivo dissection of direct RFX-target gene promoters in C. elegans reveals a novel cis-regulatory element, the C-box.

    Science.gov (United States)

    Burghoorn, Jan; Piasecki, Brian P; Crona, Filip; Phirke, Prasad; Jeppsson, Kristian E; Swoboda, Peter

    2012-08-15

    At the core of the primary transcriptional network regulating ciliary gene expression in Caenorhabditis elegans sensory neurons is the RFX/DAF-19 transcription factor, which binds and thereby positively regulates 13-15 bp X-box promoter motifs found in the cis-regulatory regions of many ciliary genes. However, the variable expression of direct RFX-target genes in various sets of ciliated sensory neurons (CSNs) occurs through as of yet uncharacterized mechanisms. In this study the cis-regulatory regions of 41 direct RFX-target genes are compared using in vivo genetic analyses and computational comparisons of orthologous nematode sequences. We find that neither the proximity to the translational start site nor the exact sequence composition of the X-box promoter motif of the respective ciliary gene can explain the variation in expression patterns observed among different direct RFX-target genes. Instead, a novel enhancer element appears to co-regulate ciliary genes in a DAF-19 dependent manner. This cytosine- and thymidine-rich sequence, the C-box, was found in the cis-regulatory regions in close proximity to the respective X-box motif for 84% of the most broadly expressed direct RFX-target genes sampled in this study. Molecular characterization confirmed that these 8-11 bp C-box sequences act as strong enhancer elements for direct RFX-target genes. An artificial promoter containing only an X-box promoter motif and two of the C-box enhancer elements was able to drive strong expression of a GFP reporter construct in many C. elegans CSNs. These data provide a much-improved understanding of how direct RFX-target genes are differentially regulated in C. elegans and will provide a molecular model for uncovering the transcriptional network mediating ciliary gene expression in animals. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. A suggestion to improve a day keeps your depletion away: Examining promotive and prohibitive voice behaviors within a regulatory focus and ego depletion framework.

    Science.gov (United States)

    Lin, Szu-Han Joanna; Johnson, Russell E

    2015-09-01

    One way that employees contribute to organizational effectiveness is by expressing voice. They may offer suggestions for how to improve the organization (promotive voice behavior), or express concerns to prevent harmful events from occurring (prohibitive voice behavior). Although promotive and prohibitive voices are thought to be distinct types of behavior, very little is known about their unique antecedents and consequences. In this study we draw on regulatory focus and ego depletion theories to derive a theoretical model that outlines a dynamic process of the antecedents and consequences of voice behavior. Results from 2 multiwave field studies revealed that promotion and prevention foci have unique ties to promotive and prohibitive voice, respectively. Promotive and prohibitive voice, in turn, were associated with decreases and increases, respectively, in depletion. Consistent with the dynamic nature of self-control, depletion was associated with reductions in employees' subsequent voice behavior, regardless of the type of voice (promotive or prohibitive). Results were consistent across 2 studies and remained even after controlling for other established antecedents of voice and alternative mediating mechanisms beside depletion. (c) 2015 APA, all rights reserved).

  4. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Science.gov (United States)

    Nguyen, Margaret U; Kwong, Jereen; Chang, Julia; Gillet, Victoria G; Lee, Rachel M; Johnson, Karl Gregory

    2016-01-01

    The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  5. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Margaret U Nguyen

    Full Text Available The heparan sulfate proteoglycan (HSPG Syndecan (Sdc is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ. To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  6. Promoting Prosocial Behavior and Self-Regulatory Skills in Preschool Children through a Mindfulness-Based Kindness Curriculum

    Science.gov (United States)

    Flook, Lisa; Goldberg, Simon B.; Pinger, Laura; Davidson, Richard J.

    2015-01-01

    Self-regulatory abilities are robust predictors of important outcomes across the life span, yet they are rarely taught explicitly in school. Using a randomized controlled design, the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum (KC) delivered in a public school setting on executive function,…

  7. Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report

    NARCIS (Netherlands)

    Meiler, Svenja; Smeets, Esther; Winkels, Holger; Shami, Annelie; Pascutti, Maria Fernanda; Nolte, Martijn A.; Beckers, Linda; Weber, Christian; Gerdes, Norbert; Lutgens, Esther

    2016-01-01

    Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4(+) effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood. Low-density lipoprotein

  8. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model.

    Science.gov (United States)

    Wildenberg, Manon E; Levin, Alon D; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J; Hakvoort, Theodorus B M; Westera, Liset; Bloemendaal, Felicia M; Brandse, Johannan F; Simmons, Alison; D'Haens, Geert R; Ebner, Daniel; van den Brink, Gijs R

    2017-12-04

    Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the combination of anti-TNF and thiopurines, consistent with the enhanced efficacy of this combination therapy described in clinical trials. As thiopurines are unfortunately associated with significant side effects, we here aimed to identify alternatives for combination therapy with anti-TNF, using the macrophage induction model as a screening tool. Mixed lymphocyte reactions were treated with anti-TNF and a library of 1600 drug compounds. Induction of CD14+CD206+ macrophages was analysed by flow cytometry. Positive hits were validated in vitro and in the T cell transfer model of colitis. Among the 98 compounds potentiating the induction of regulatory macrophages by anti-TNF were six benzimidazoles, including albendazole. Albendazole treatment in the presence of anti-TNF resulted in alterations in the tubulin skeleton and signalling though AMPK, which was required for the enhanced induction. Combination therapy also increased expression levels of the immunoregulatory cytokine IL-10. In vivo, albendazole plus anti-TNF combination therapy was superior to monotherapy in a model of colitis, in terms of both induction of regulatory macrophages and improvement of clinical symptoms. Albendazole enhances the induction of regulatory macrophages by anti-TNF and potentiates clinical efficacy in murine colitis. Given its favourable safety profile, these data indicate that the repurposing of albendazole may be a novel option for anti-TNF combination therapy in IBD.

  9. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype.

    Science.gov (United States)

    De Oliveira, Tiago; Abiatari, Ivane; Raulefs, Susanne; Sauliunaite, Danguole; Erkan, Mert; Kong, Bo; Friess, Helmut; Michalski, Christoph W; Kleeff, Jörg

    2012-04-03

    We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC) cells. Syndecan-2 (SDC-2) expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides) did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and--further downstream--phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. SDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  10. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    De Oliveira Tiago

    2012-04-01

    Full Text Available Abstract Background We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC cells. Methods Syndecan-2 (SDC-2 expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. Results SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. Conclusion SDC-2 is a novel (perineural invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  11. MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation.

    Science.gov (United States)

    Lee, Kyung-Min; Giltnane, Jennifer M; Balko, Justin M; Schwarz, Luis J; Guerrero-Zotano, Angel L; Hutchinson, Katherine E; Nixon, Mellissa J; Estrada, Mónica V; Sánchez, Violeta; Sanders, Melinda E; Lee, Taekyu; Gómez, Henry; Lluch, Ana; Pérez-Fidalgo, J Alejandro; Wolf, Melissa Magdalene; Andrejeva, Gabriela; Rathmell, Jeffrey C; Fesik, Stephen W; Arteaga, Carlos L

    2017-10-03

    Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of activated mtOXPHOS, led to the accumulation of HIF-1α. Pharmacological inhibition of HIF-1α attenuated CSC enrichment and tumor initiation in vivo. These data suggest that (1) MYC and MCL1 confer resistance to chemotherapy by expanding CSCs via mtOXPHOS and (2) targeting mitochondrial respiration and HIF-1α may reverse chemotherapy resistance in TNBC. Copyright © 2017. Published by Elsevier Inc.

  12. Using group learning to promote integration and cooperative learning between Asian and Australian second-year veterinary science students.

    Science.gov (United States)

    Mills, Paul C; Woodall, Peter F; Bellingham, Mark; Noad, Michael; Lloyd, Shan

    2007-01-01

    There is a tendency for students from different nationalities to remain within groups of similar cultural backgrounds. The study reported here used group project work to encourage integration and cooperative learning between Australian students and Asian (Southeast Asian) international students in the second year of a veterinary science program. The group project involved an oral presentation during a second-year course (Structure and Function), with group formation engineered to include very high, high, moderate, and low achievers (based on previous grades). One Asian student and three Australian students were placed in each group. Student perceptions of group dynamics were analyzed through a self-report survey completed at the end of the presentations and through group student interviews. Results from the survey were analyzed by chi-square to compare the responses between Asian and Australian students, with statistical significance accepted at p learning experience. Asian students expressed a greater preference for working in a group than for working alone (p = 0.001) and reported more frequently than Australian students that teamwork produces better results (p = 0.01). Australian students were more likely than Asian students to voice their opinion in a team setting (p = 0.001), while Asian students were more likely to depend on the lecturer for directions (p = 0.001). The results also showed that group project work appeared to create an environment that supported learning and was a successful strategy to achieve acceptance of cultural differences.

  13. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

    Science.gov (United States)

    Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

    2016-10-01

    DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. © The Author(s).

  14. Report on the research cooperation promoting project in fiscal 1998. Research cooperation related to the mine waste water treatment technology utilizing biomass; 1998 nendo kenkyu kyoryoku suishin jigyo hokokusho. Bio riyo ni yoru kohaisui shori gijutsu ni kansuru kyoryoku

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    This paper describes the achievement in relation with the mine waste water treatment technology utilizing biomass, from among the promotion projects for research cooperation with China. Waste water is converted into ferric iron (Fe{sup 3+}), which precipitates at low pH, by utilizing iron oxidizing bacteria which use ferrous iron (Fe{sup 2+}) in the waste water as the energy source, and is precipitated and removed by using low-cost calcium carbonate as a neutralizing agent. Fiscal 1998 has performed eight site surveys with 47 persons in total. The main survey items are the study and guidance of pilot plant operation and the survey on measures to prevent occurrence of contamination by heavy metals in Wushan Mine. Additional site surveys were made at Dexing Mine and Yinshan Lead/Zinc Mine. Continued from fiscal 1997, consumables required for the pilot plant were purchased, and items of the bench-scale testing equipment used by Japan for domestic researches (an oxidation and neutralization testing equipment and a copper recovering and testing equipment) were transported to China. The operation research data of the pilot plant were put in order and analyzed. This paper summarizes the concept design of the shaft waste water treatment facilities for the north mine in Wushan Mine, and the surveys on measures for heavy metal contamination sources. (NEDO)

  15. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling

    Directory of Open Access Journals (Sweden)

    Grusche Felix A

    2011-09-01

    Full Text Available Abstract Background Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship. Results Here we show in Drosophila that loss of Scribbled (Scrib, a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc. scrib mutant tissue overgrowth, but not the loss of cell polarity, is dependent upon defective Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family transcription factor Scalloped or the transcriptional coactivator Yorkie in the eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and Yorkie-Scalloped activity is required to promote this cooperative tumor overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is not dependent upon JNK activity, but can be significantly rescued by reducing aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote increased Hippo signaling, suggesting that aPKC activity is not normally rate limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo pathway inhibition in scrib mutants occurs, at least in part, downstream or in parallel to both the Expanded and Fat arms of Hippo pathway regulation. Conclusions Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue

  16. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

    Directory of Open Access Journals (Sweden)

    Huang Xiangsheng

    2012-12-01

    Full Text Available Abstract Background The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. Methods We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25 in Gabonese individuals exposed to plentiful parasitic infections. Results We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576 for IL2 and -409C/T (ss410961577 for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (Prs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein and C/EBP beta (CCAAT/enhancer binding protein beta that are believed to regulate the Treg function. Conclusions The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

  17. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population.

    Science.gov (United States)

    Huang, Xiangsheng; Kühne, Vera; Kun, Jürgen F J; Soboslay, Peter T; Lell, Bertrand; Tp, Velavan

    2012-12-07

    The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function. The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

  18. Cooperative Learning: Developments in Research

    Science.gov (United States)

    Gillies, Robyn M.

    2014-01-01

    Cooperative learning is widely recognized as a pedagogical practice that promotes socialization and learning among students from kindergarten through to college level and across different subject areas. Cooperative learning involves students working together to achieve common goals or complete group tasks. Interest in cooperative learning has…

  19. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the Comprehensive Nuclear-Test-Ban Treaty. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Okko, O. (ed.)

    2012-07-01

    The regulatory control of nuclear materials (i.e. nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. Safeguards are required for Finland to comply with international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). The results of STUK's nuclear safeguards inspection activities in 2011 continued to demonstrate that the Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations.

  20. GNAS(R201H) and Kras(G12D) cooperate to promote murine pancreatic tumorigenesis recapitulating human intraductal papillary mucinous neoplasm.

    Science.gov (United States)

    Taki, K; Ohmuraya, M; Tanji, E; Komatsu, H; Hashimoto, D; Semba, K; Araki, K; Kawaguchi, Y; Baba, H; Furukawa, T

    2016-05-05

    Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that mediates a stimulatory signal to adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), subsequently activating cAMP-dependent protein kinase A. The GNAS(R201H) mutation results in constitutive activation of Gsα. To study the potential role of GNAS in pancreatic tumorigenesis in vivo, we generated lines of transgenic mice in which the transgene consisted of Lox-STOP-Lox (LSL)-GNAS(R201H) under the control of the CAG promoter (Tg(CAG-LSL-GNAS)). These mice were crossed with pancreatic transcription factor 1a (Ptf1a)-Cre mice (Ptf1a(Cre/+)), generating Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice. This mouse line showed elevated cAMP levels, small dilated tubular complex formation, loss of acinar cells and fibrosis in the pancreas; however, no macroscopic tumorigenesis was apparent by 2 months of age. We then crossed Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice with LSL-Kras(G12D) mice, generating Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice. We used these mice to investigate a possible cooperative effect of GNAS(R201H) and Kras(G12D) in pancreatic tumorigenesis. Within 5 weeks, Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice developed a cystic tumor consisting of marked dilated ducts lined with papillary dysplastic epithelia in the pancreas, which closely mimicked the human IPMN. Our data strongly suggest that activating mutations in GNAS and Kras cooperatively promote murine pancreatic tumorigenesis, which recapitulates IPMN. Our mouse model may serve as a unique in vivo platform to find biomarkers and effective drugs for diseases associated with GNAS mutations.

  1. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation.

    Science.gov (United States)

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing

    2015-07-01

    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  2. Cis-regulatory PLETHORA promoter elements directing root and nodule expression are conserved between Arabidopsis thaliana and Medicago truncatula.

    Science.gov (United States)

    Franssen, Henk J; Kulikova, Olga; Willemsen, Viola; Heidstra, Renze

    2017-02-01

    Nodules are unique organs formed on roots of legumes by soil-borne bacteria, collectively known as rhizobium. Recently, we have shown that orthologs of the AINTEGUMENTA-like (AIL) AP2 transcription factors PLETHORA (PLT) 1 to 4, that redundantly regulate Arabidopsis thaliana root development are involved in root and nodule growth in Medicago truncatula. Hence, it is conceivable that rhizobium has co-opted these genes for nodule development. Whether this co-option requires the presence of specific cis-elements in the promoters and/or specialization of PLT protein function is not clear. Here, we analyzed the qualitative expression patterns of the Arabidopsis PLT1 to 4 promoters in Medicago roots and nodules and compared these with the described expression patterns of the Medicago PLT genes. Our studies reveal that the expression patterns of the investigated promoters and their Medicago orthologs are very similar, indicating that at least all cis-elements regulating spatial PLT expression are conserved among the Arabidopsis and Medicago PLT1 to 4 promoters.

  3. Regulatory elements in the promoter region of the rat gene encoding the acyl-CoA-binding protein

    DEFF Research Database (Denmark)

    Elholm, M; Bjerking, G; Knudsen, J

    1996-01-01

    Acyl-CoA-binding protein (ACBP) is an ubiquitously expressed 10-kDa protein which is present in high amounts in cells involved in solute transport or secretion. Rat ACBP is encoded by a gene containing the typical hallmarks of a housekeeping gene. Analysis of the promoter region of the rat ACBP g...

  4. Promoting Risk-Taking and Physically Challenging Play in Australian Early Childhood Settings in a Changing Regulatory Environment

    Science.gov (United States)

    Little, Helen

    2017-01-01

    This article presents data from a survey of Early Childhood Education and Care services in Australia. The study investigated outdoor play provision in terms of space, resources and planning for risk-taking in play. Overall, the results indicate that the participating centres are well-resourced to promote physical play, but vary in terms of…

  5. G-quadruplex forming structural motifs in the genome of Deinococcus radiodurans and their regulatory roles in promoter functions.

    Science.gov (United States)

    Kota, Swathi; Dhamodharan, V; Pradeepkumar, P I; Misra, Hari S

    2015-11-01

    Deinococcus radiodurans displays compromised radioresistance in the presence of guanine quadruplex (G4)-binding drugs (G4 drugs). Genome-wide scanning showed islands of guanine runs (G-motif) in the upstream regions of coding sequences as well as in the structural regions of many genes, indicating a role for G4 DNA in the regulation of genome functions in this bacterium. G-motifs present upstream to some of the DNA damage-responsive genes like lexA, pprI, recF, recQ, mutL and radA were synthesized, and the formation of G4 DNA structures was probed in vitro. The G-motifs present at the 67th position upstream to recQ and at the 121st position upstream to mutL produced parallel and mixed G4 DNA structures, respectively. Expression of β-galactosidase under recQ and mutL promoters containing respective G-motifs was inhibited by G4 drugs under normal growth conditions in D. radiodurans. However, when such cells were exposed to γ radiation, mutL promoter activity was stimulated while recQ promoter activity was inhibited in the presence of G4 drugs. Deletion of the G-motif from the recQ promoter could relax it from G4 drug repression. D. radiodurans cells treated with G4 drug showed reduction in recQ expression and γ radiation resistance, indicating an involvement of G4 DNA in the radioresistance of this bacterium. These results suggest that G-motifs from D. radiodurans genome form different types of G4 DNA structures at least in vitro, and the recQ and mutL promoters seem to be differentially regulated at the levels of G4 DNA structures.

  6. Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

    Directory of Open Access Journals (Sweden)

    Rohimah Mohamud

    2017-12-01

    Full Text Available Synthetic glycine coated 50 nm polystyrene nanoparticles (NP (PS50G, unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2 expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.

  7. Phage phi 29 regulatory protein p4 stabilizes the binding of the RNA polymerase to the late promoter in a process involving direct protein-protein contacts.

    Science.gov (United States)

    Nuez, B; Rojo, F; Salas, M

    1992-12-01

    Transcription from the late promoter, PA3, of Bacillus subtilis phage phi 29 is activated by the viral regulatory protein p4. A kinetic analysis of the activation process has revealed that the role of protein p4 is to stabilize the binding of RNA polymerase to the promoter as a closed complex without significantly affecting further steps of the initiation process. Electrophoretic band-shift assays performed with a DNA fragment spanning only the protein p4 binding site showed that RNA polymerase could efficiently retard the complex formed by protein p4 bound to the DNA. Similarly, when a DNA fragment containing only the RNA polymerase-binding region of PA3 was used, p4 greatly stimulated the binding of RNA polymerase to the DNA. These results strongly suggest that p4 and RNA polymerase contact each other at the PA3 promoter. In the light of current knowledge of the p4 activation mechanism, we propose that direct contacts between the two proteins participate in the activation process.

  8. Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Liqing Wang

    2016-11-01

    Full Text Available Foxp3+ T-regulatory (Treg cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or “secondary” modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3. Genetic or pharmacologic targeting of Usp7 impairs Foxp3+ Treg suppressive functions, while conventional T cell responses remain intact. As a result, pharmacologic inhibitors of Usp7 can limit tumor growth in immunocompetent mice, and promote the efficacy of antitumor vaccines and immune checkpoint therapy with anti-PD1 monoclonal antibody in murine models. Hence, pharmacologic therapy with Usp7 inhibitors may have an important role in future cancer immunotherapy.

  9. Inducible CTCF insulator delays the IgH 3' regulatory region-mediated activation of germline promoters and alters class switching.

    Science.gov (United States)

    Braikia, Fatima-Zohra; Oudinet, Chloé; Haddad, Dania; Oruc, Zeliha; Orlando, Domenico; Dauba, Audrey; Le Bert, Marc; Khamlichi, Ahmed Amine

    2017-06-06

    Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3'RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3'RR in developing B cells.

  10. Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology

    Science.gov (United States)

    Swieboda, David P.

    2017-01-01

    Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27. PMID:28953978

  11. Using Tracking Data to Promote Environmental Public Health Through Regulatory and Legislative Processes in New York City.

    Science.gov (United States)

    McKelvey, Wendy; Blank, Jeffrey; Kheirbek, Iyad; Torin, Beth

    Legislation and regulation are powerful tools for decreasing health risks from environmental hazards. Legislation is enacted by an elected body, and regulations are issued by an agency in the executive branch delegated authority by the legislature to carry out enacted laws. The New York City (NYC) Environmental Public Health Tracking Program makes data and analytic findings available to policy makers to inform development of sound and effective environmental health legislation and regulation. Tracking data and associated science create awareness of environmental hazards and health impacts, guide strategies for mitigating hazards, and sustain support for effective law by documenting beneficial impacts on the environment and health. We describe how environmental and health surveillance data and analytic findings have informed legislation and regulations related to restaurant food safety and air pollution control in NYC. Using data to guide legislative and regulatory processes helps ensure that policy decisions and directions are based on objective evidence.

  12. CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in skin

    Science.gov (United States)

    Xia, Mingcan; Hu, Shaomin; Fu, Yaoyao; Jin, Wensen; Yi, Qiyi; Matsui, Yurika; Yang, Jie; McDowell, Mary Ann; Sarkar, Surojit; Kalia, Vandana; Xiong, Na

    2014-01-01

    Background CCR10 and CCL27 are the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases including atopic dermatitis and psoriasis. This pair is thought to regulate migration and/or maintenance of skin T cells and suggested as therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. Objective We sought to determine expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into potential roles of CCR10 during skin inflammation. Methods Using heterozygous and homozygous CCR10-knockout/EGFP-knockin mice, we assessed expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens and auto-reactive T cells. In addition, we assessed the effect of CCR10-knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. Results CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10-knockout mice, the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmamia infection in the skin. Conclusion CCR10 is a critical regulator of skin immune homeostasis. PMID:24767879

  13. The role of the legislative and regulatory branches in promoting the use of geothermal energy in Latvia

    OpenAIRE

    I. Skapare; A. Kreslins; Cers, A

    2016-01-01

    Latvia currently is self-sufficient in energy resources up to approximately 35 %. Annual fossil energy prices rise and risks of security of energy supply promote the development legislation in the matter of renewable resources. One of the Latvian Ministry of Economics' recent products is a new draft law called the "Renewable Energy Law", which has been created due to one of the European Union and Latvian national energy policy objectives: to increase the share of renewable e...

  14. Capping protein regulatory cycle driven by CARMIL and V-1 may promote actin network assembly at protruding edges.

    Science.gov (United States)

    Fujiwara, Ikuko; Remmert, Kirsten; Piszczek, Grzegorz; Hammer, John A

    2014-05-13

    Although capping protein (CP) terminates actin filament elongation, it promotes Arp2/3-dependent actin network assembly and accelerates actin-based motility both in vitro and in vivo. In vitro, capping protein Arp2/3 myosin I linker (CARMIL) antagonizes CP by reducing its affinity for the barbed end and by uncapping CP-capped filaments, whereas the protein V-1/myotrophin sequesters CP in an inactive complex. Previous work showed that CARMIL can readily retrieve CP from the CP:V-1 complex, thereby converting inactive CP into a version with moderate affinity for the barbed end. Here we further clarify the mechanism of this exchange reaction, and we demonstrate that the CP:CARMIL complex created by complex exchange slows the rate of barbed-end elongation by rapidly associating with, and dissociating from, the barbed end. Importantly, the cellular concentrations of V-1 and CP determined here argue that most CP is sequestered by V-1 at steady state in vivo. Finally, we show that CARMIL is recruited to the plasma membrane and only at cell edges undergoing active protrusion. Assuming that CARMIL is active only at this location, our data argue that a large pool of freely diffusing, inactive CP (CP:V-1) feeds, via CARMIL-driven complex exchange, the formation of weak-capping complexes (CP:CARMIL) at the plasma membrane of protruding edges. In vivo, therefore, CARMIL should promote Arp2/3-dependent actin network assembly at the leading edge by promoting barbed-end capping there.

  15. Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Marco Tucci

    2010-01-01

    Full Text Available Lupus nephritis (LN occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th- 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

  16. Interleukin-10 deficiency impairs regulatory T cell-derived neuropilin-1 functions and promotes Th1 and Th17 immunity.

    Science.gov (United States)

    Wang, Shimin; Gao, Xiang; Shen, Guobo; Wang, Wei; Li, Jingyu; Zhao, Jingyi; Wei, Yu-Quan; Edwards, Carl K

    2016-04-14

    Regulatory T cells (Tregs) expand in peripheral lymphoid organs and can produce immunosuppressive cytokines to support tumor growth. IL-10 abrogation efficiently induces Treg formation but dampens tumoral neuropilin-1 (Nrp-1) Treg signaling, which simultaneously augments Th1 and Th17 immunity. These effects are associated with the plasticity and stability of Tregs and effector T cell functions that can limit tumorigenesis. Within the tumor microenvironment, there appears to be a "mutual antagonism" between immunoenhancement and immunosuppression mechanisms, eventually leading to decreased metastasis. In contrast, tumor progression is paralleled by a reduction in Nrp-1-producing Tregs controlled by the IL-10 and TGF-β1 levels. However, Th1, Th17 and Treg immunity is primarily regulated by IL-10 or Nrp-1 and not TGF-β1 except when combined with IL-10. These results emphasize the important implications for the therapeutic use of Tregs. The number of Treg cells must be maintained in a healthy and dynamic homeostatic range to prevent malignant diseases. Moreover, Treg-mediated immunosuppression can be limited by reducing tumor-derived Treg Nrp-1 levels.

  17. The role of the legislative and regulatory branches in promoting the use of geothermal energy in Latvia

    Science.gov (United States)

    Skapare, I.; Kreslins, A.; Cers, A.

    2016-09-01

    Latvia currently is self-sufficient in energy resources up to approximately 35 %. Annual fossil energy prices rise and risks of security of energy supply promote the development legislation in the matter of renewable resources. One of the Latvian Ministry of Economics' recent products is a new draft law called the "Renewable Energy Law", which has been created due to one of the European Union and Latvian national energy policy objectives: to increase the share of renewable energy up to 40 % by 2020 (Moore and Vanags, 2012). Currently, geothermal energy potential is assessed at 1 × 1013 kWh; nevertheless, it is difficult for geothermal energy to compete with other renewable energy resources in the Latvian energy market. A great job has been done in recent years at the legislative branch to choose the right methods for supporting the use of renewable energy resources. This paper aims is analysis of current situation and assessment of Latvian legislation possibilities to promote the use of geothermal energy.

  18. Hydrogen Sulfide Promotes Tet1- and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis.

    Science.gov (United States)

    Yang, Ruili; Qu, Cunye; Zhou, Yu; Konkel, Joanne E; Shi, Shihong; Liu, Yi; Chen, Chider; Liu, Shiyu; Liu, Dawei; Chen, Yibu; Zandi, Ebrahim; Chen, Wanjun; Zhou, Yanheng; Shi, Songtao

    2015-08-18

    Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-β (TGF-β)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-β and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Scientific and Regulatory Policy Committee Review: Review of the Organisation for Economic Co-operation and Development (OECD) Guidance on the GLP Requirements for Peer Review of Histopathology.

    Science.gov (United States)

    Fikes, James D; Patrick, Daniel J; Francke, Sabine; Frazier, Kendall S; Reindel, James F; Romeike, Annette; Spaet, Robert H; Tomlinson, Lindsay; Schafer, Kenneth A

    2015-10-01

    In 2014, the Organisation for Economic Co-operation and Development (OECD) issued guidance no. 16, Guidance on the GLP Requirements for Peer Review of Histopathology. The stated purpose of the guidance document is "to provide guidance to pathologists, test facility management, study directors and quality assurance personnel on how the peer review of histopathology should be planned, managed, documented, and reported in order to meet Good Laboratory Practice (GLP) expectations and requirements." On behalf of and in collaboration with the global societies of toxicologic pathology, the Society of Toxicologic Pathology initiated a review of OECD guidance no. 16. The objectives of this review are to provide a unified interpretation of the guidance, to recommend compliant processes for organizations to implement, and to avoid inconsistent process adaptations across the industry. This review of the guidance document is the product of a global collaboration with other societies of toxicologic pathology and provides a section-by-section international consensus view and interpretation of the OECD guidance on peer review. © 2015 by The Author(s).

  20. Regulatory Promotion of Waste Wood Reused as an Energy Source and the Environmental Concerns about Ash Residue in the Industrial Sector of Taiwan

    Directory of Open Access Journals (Sweden)

    Wen-Tien Tsai

    2012-11-01

    Full Text Available The objective of this paper was to provide a preliminary analysis of the utilization of energy derived from waste wood in Taiwan, a highly industrialized country with a high dependence (over 99% on imported energy. The discussion focuses on the status of waste wood generation and its management over the past decade. Findings show that the quantities of biomass waste collected for reuse purposes in the industrial sectors of Taiwan has exhibited an increasing trend, from about 4000 tons in 2001 to over 52,000 tons in 2010. Although waste wood can be reused as a fuel and raw material for a variety of applications based on regulatory promotion, the most commonly used end use is to directly utilize it as an auxiliary fuel in industrial utilities (e.g., boilers, heaters and furnaces for the purpose of co-firing with coal/fuel oil. The most progressive measure for promoting biomass-to-power is to introduce the feed-in tariff (FIT mechanism according to the Renewable Energy Development Act passed in June 2009. The financial support for biomass power generation has been increasing over the years from 0.070 US$/kWh in 2010 to 0.094 US$/kWh in 2012. On the other hand, the environmental regulations in Taiwan regarding the hazard identification of wood-combusted ash (especially in filter fly-ash and its options for disposal and utilization are further discussed in the paper, suggesting that waste wood impregnated with chromated copper arsenate (CCA and other copper-based preservatives should be excluded from the wood-to-energy system. Finally, some recommendations for promoting wood-to-energy in the near future of Taiwan are addressed.

  1. The implications of the marketing promotional compound in a cooperative of the rural electrification: the case of CERTAJA-RS; As implicacoes do composto promocional de marketing numa cooperativa de eletrificacao rural: o caso da CERTAJA-RS

    Energy Technology Data Exchange (ETDEWEB)

    Sluszz, Thaisy; Padilha, Ana Claudia Machado; Silva, Tania Nunes da; Mattos, Paloma [UniversidadeFederal do Rio Grande do Sul (CEPAN-UFRGS), Porto Alegre, RS (Brazil). Centro de Estudos e Pesquisas em Agronegocios

    2006-07-01

    The present study it consisted of analyzing the made up of marketing of the cooperative of agricultural electrification - CERTAJA, aiming at to identify which is the current actions developed and implemented for the cooperative. For this, it was used as analysis object the tools of the made up of marketing, the 4 P's (product, price, point of distribution and promotion), that it was identified by means of questionnaires saw e-mail to the manager of the department of energy, to the vice president, to the responsible one for the financial department and to the assessorship of the press that has fort linking with the department of marketing. As main results it is cited consolidation of communication channels that offer possibility to the social picture to participate of the decisions of the cooperative, as well as having information for way written and said decisions to them of management and administration. The supply of electric energy has as focus the satisfaction of the cooperated ones that they are partner-proprietors of the cooperative, being excellent to offer to these and excessively consuming a product or service that takes care of to its expectations. (author)

  2. Strategies for patient empowerment through the promotion of medicines in Israel: regulatory framework for the pharmaceutical industry.

    Science.gov (United States)

    Schwartzberg, Eyal; Barnett-Itzhaki, Zohar; Grotto, Itamar; Marom, Eli

    2017-09-29

    The correct and rational use of medications can have a positive direct impact on disease outcomes, as well on the utilization of the health system resources. Unfortunately, 50% of the patients do not take their medications as prescribed, largely due to lack of patients' understanding of their medical condition, as well as the lack of reliable medicine information.There are multiple strategies implemented in many countries to tackle this challenge including: disease awareness campaigns (DAC) to raise the public awareness to specific diseases, direct-to-consumer advertisement (DTCA) to raise the public awareness to prescription medicines, specific treatments and over-the-counter (OTC) products to improve the accessibility of patients to specific medicines.Prior to 2013, the Israeli policy prohibited prescribing medication advertising and prevented the flow of information from pharmaceutical companies to the patient. In the last five years, the Pharmaceutical division in the Israeli Ministry of Health, as part of the "empowering the patient" agenda, has taken new innovative approaches to raise public awareness to diseases, medications and appropriate usage, as well as promotion of information to improve patient adherence to the prescribed medication.This paper elaborates on the aforementioned strategies implemented in developed countries, and specifically focuses on newly implemented strategies and regulations in Israel regarding pre- and post-prescription information, to improve patient appropriate utilization and adherence to medication.

  3. Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti-melanoma immune response.

    Science.gov (United States)

    Sarrabayrouse, Guillaume; Pich, Christine; Teiti, Iotefa; Tilkin-Mariame, Anne Françoise

    2017-02-15

    Melanoma is a highly lethal cutaneous tumor, killing affected patients through development of multiple poorly immunogenic metastases. Suboptimal activation of immune system by melanoma cells is often due to molecular modifications occurring during tumor progression that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases. They are also known to inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases are regarded as molecular switches that regulate a wide spectrum of cellular functions and their dysfunction has been characterized in various oncogenic process notably in melanoma progression. Moreover, these molecules can modulate the immune response. Since 10 years we have demonstrated that Statins and other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and innate anti-melanoma immune response. In this review we summarize our major observations demonstrating that these pharmacological agents stimulate melanoma immunogenicity and suggest a potential use of these molecules to promote anti-melanoma immune response. © 2016 UICC.

  4. Progress report on the regulatory cooperation program between the Norwegian Radiation Protection Authority and the Federal Medical Biological Agency of Russia. Final report of projects and other activities completed in 2008-2009 and plans for 2010-2011

    Energy Technology Data Exchange (ETDEWEB)

    Roudak, S. F.; Sneve, M. K.; Kiselev, M.; Shandala, N. K.

    2011-06-15

    This report sets out the progress made in the projects and related activities carried out in the period 2008 - 2009 within the Regulatory Cooperation Program between the Norwegian Radiation Protection Authority and the Federal Medical Biological Agency of Russia. The progress described follows directly from previous work carried out within the Regulatory Cooperation Program, as set out in earlier NRPA reports and in accordance with the Norwegian Government's Plan of Action to improve nuclear and radiation safety in Northwest Russia. The work was carried out by specialists of the Burnasyan Federal Medical Biophysical Centre, with support from other Russian organisations and specialists as well as experts from the NRPA. Five main projects are described, each of which has contributed to the improvement of regulatory supervision by the FMBA over the sites operated by SevRAO in the Northwest of Russia, including the Sites for Temporary Storage at Andreyev Bay and Gremikha, and the Regional Centre for Waste Conditioning and Long-term Storage at Saida Bay. The main activities of interest include recovery and secure the safe condition of spent nuclear fuel and radioactive waste from inadequate storage facilities and ensuring their continued future safe storage. The topics covered by these projects include: Control of Occupational Exposure and Optimisation During Hazardous Operations through the Development of Databases on Radiation Situation and Individual Occupational Exposure (DOSEMAP). The software for a mapping database of radiation situation parameters at SevRAO Facilities has been developed. A computer scheme of workshops in new Complex facilities for the spent nuclear fuel and radioactive waste management, the design of which is already available, has been developed. The software for the database on individual doses to the SevRAO workers has also been developed. Two draft guidance documents have been prepared: 'Application of the database on the radiation

  5. Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice.

    Directory of Open Access Journals (Sweden)

    Jinlin Liu

    Full Text Available BACKGROUND: Tumor-associated macrophages (TAMs remodel the colorectal cancer (CRC microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3(+ regulatory T (Treg-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: CRC was either induced by N-methyl-N-nitrosourea (MNU and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93 in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3(GFP+ Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. CONCLUSIONS/SIGNIFICANCE: TAMs recruit CCR6(+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model.

  6. IL-10-Producing B Cells Suppress Effector T Cells Activation and Promote Regulatory T Cells in Crystalline Silica-Induced Inflammatory Response In Vitro

    Directory of Open Access Journals (Sweden)

    Yiping Lu

    2017-01-01

    Full Text Available Long-term exposure to crystalline silica leads to silicosis, which is characterized by persistent lung inflammation and lung fibrosis. Multiple immune cells have been demonstrated to participate in crystalline silica-induced immune responses. Our previous study indicated that B10 could control lung inflammation through modulating the Th balance in experimental silicosis in mice. However, the regulatory mechanism of B10 on CD4+ T cells is still unclear. MACS-sorted CD19+ B cells from the three different groups were cultured with CD4+ T cells either with or without transwell insert plates to evaluate the effects of B10 on CD4+ T cells, including Teff and Treg. B10 was eliminated by anti-CD22 application in vivo. Flow cytometry was used to test the frequencies of CD4+ T cells, and the expressions of the related cytokines were detected by real-time PCR and CBA. Insufficient B10 elevated the levels of proinflammatory cytokines and promoted Th responses in a way independent upon cell-cell contact in the Teff and B cell coculture system. B10 could both increase Treg activity and enhance conversion of Teff into Treg. Our findings demonstrated that B10 could affect Th responses by the release of IL-10, enhancing Treg functions and converting Teff into Treg.

  7. A Novel Sucrose-Regulatory MADS-Box Transcription Factor GmNMHC5 Promotes Root Development and Nodulation in Soybean (Glycine max [L.] Merr.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2015-08-01

    Full Text Available The MADS-box protein family includes many transcription factors that have a conserved DNA-binding MADS-box domain. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily in root development, have greatly broadened their known functions. In this study, a gene from soybean (Glycine max [L.] Merr., GmNMHC5, was cloned from the Zigongdongdou cultivar and identified as a member of the AGL17 subfamily. Real-time fluorescence quantitative PCR analysis showed that GmNMHC5 was expressed at much higher levels in roots and nodules than in other organs. The activation of expression was first examined in leaves and roots, followed by shoot apexes. GmNMHC5 expression levels rose sharply when the plants were treated under short-day conditions (SD and started to pod, whereas low levels were maintained in non-podding plants under long-day conditions (LD. Furthermore, overexpression of GmNMHC5 in transgenic soybean significantly promoted lateral root development and nodule building. Moreover, GmNMHC5 is upregulated by exogenous sucrose. These results indicate that GmNMHC5 can sense the sucrose signal and plays significant roles in lateral root development and nodule building.

  8. Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis.

    Science.gov (United States)

    Pu, Jun; Zhang, Xiaorui; Luo, Huiwen; Xu, Lijuan; Lu, Xiaozhao; Lu, Jianguo

    2017-11-25

    Psychological stress has recently been described as a risk factor in the development of pancreatic cancer. Here, we reported that increased neurotransmitter adrenaline was associated with the poor survival in pancreatic cancer patients. Moreover, in the cell model study, we found adrenaline promoted pancreatic cell PANC-1 migration in a dose dependent manner. Block of the β2-adrenoreceptor with ICI118,551, significantly reduced cell migration. Further study found that adrenaline induced a cytoplasmic translocation of RNA binding protein HuR, which in turn activated TGFβ, as shown by the SBE luciferase assay and phosphorylation of Smad2/3. Either HuR knockdown or TGFβ inhibition reduced cell migration induced by adrenaline. Taken together, our study here revealed that adrenaline-HuR-TGFβ regulatory axis at least partially contributes to the psychological stress induced metastasis in PANC-1 cells, shedding light on therapeutic targeting psychological stress in improving the prognosis of pancreatic cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Interleukin 2 and interleukin 10 function synergistically to promote CD8+T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.

    Science.gov (United States)

    Li, Xiaogang; Lu, Ping; Li, Bo; Zhang, Wanfu; Yang, Rong; Chu, Yan; Luo, Kaiyuan

    2017-06-01

    The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8 + T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8 + T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8 + T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8 + T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8 + T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8 + T cells but could significantly enhance IL-2-mediated promotion of CD8 + T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8 + T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4 + CD25 + regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8 + T cells, an effect suppressible by CD4 + CD25 + Treg cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. International Clean Energy System Using Hydrogen Conversion (WE-NET). subtask 2. Research study on promotion of international cooperation; Suiso riyo kokusai clean energy system gijutsu (WE-NET). subtask 2. Kokusai kyoryoku suishin no tame no chosa kento

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This paper describes the research result on promotion of international cooperation in the WE-NET project in fiscal 1996. The WE-NET project aims at development of the total system for hydrogen production, transport, storage and utilization, and construction of the earth-friendly innovative global clean energy network integrating elemental technologies. Since the standpoint is different between latent resource supplying countries and technology supplying countries, the WE-NET project should be constantly promoted under international understanding and cooperation. The committee distributed the annual summary report prepared by NEDO to overseas organizations, and made positive PR activities in the 11th World Conference and others. The committee made the evaluation on the improvement effect of air pollution by introducing a hydrogen vehicle in combination with Stanford University, and preparation of PR video tapes for hydrogen energy. Preliminary arrangement of Internet home pages, establishment of a long-term vision for international cooperation, and proposal toward the practical WE-NET are also made. 9 figs., 13 tabs.

  11. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero

    2012-01-01

    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters ...

  12. Interferon regulatory factor 3 (IRF-3) in Japanese flounder, Paralichthys olivaceus: sequencing, limited tissue distribution, inducible expression and induction of fish type I interferon promoter.

    Science.gov (United States)

    Hu, Guobin; Yin, Xiangyan; Lou, Huimin; Xia, Jun; Dong, Xianzhi; Zhang, Jianyie; Liu, Qiuming

    2011-02-01

    Two cDNAs with different 3'-untranslated region (UTR) encoding an interferon regulatory factor 3 (IRF-3) were cloned from head kidney of Japanese flounder, Paralichthys olivaceus, by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) methods. Sequence analysis reveals that they were generated by alternative polyadenylation. The predicted protein consists of 467 amino acid residues which shares the highest identity of 50.7-57.6% to fish IRF-3 and possesses a DNA-binding domain (DBD), an IRF association domain (IAD) and a serine-rich domain (SRD) of vertebrate IRF-3. The presence of these domains along with phylogenetic analysis places it into the IRF-3 group of the IRF-3 subfamily. RT-PCR analysis revealed that flounder IRF-3 was expressed constitutively in limited tissue types including head kidney, spleen, kidney, heart, gill, intestine and liver. A quantitative real time PCR assay was employed to monitor expression of IRF-3, type I interferon (IFN) and Mx in flounder head kidney and gill. All three genes were up-regulated by polyinosinic:polycytidylic acid (polyI:C) and lymphocystis disease virus (LCDV) with an earlier but slight and less persistent increase in transcription levels seen for the IRF-3. Finally, flounder IRF-3 was proved to induce fish type I IFN promoter in FG9307 cells, a flounder gill cell line, by a luciferase assay. These results provide insights into the roles of fish IRF-3 in the antiviral immunity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Late engagement of CD86 after influenza virus clearance promotes recovery in a FoxP3+ regulatory T cell dependent manner.

    Directory of Open Access Journals (Sweden)

    Emily K Moser

    2014-08-01

    Full Text Available Influenza A virus (IAV infection in the respiratory tract triggers robust innate and adaptive immune responses, resulting in both virus clearance and lung inflammation and injury. After virus clearance, resolution of ongoing inflammation and tissue repair occur during a distinct recovery period. B7 family co-stimulatory molecules such as CD80 and CD86 have important roles in modulating T cell activity during the initiation and effector stages of the host response to IAV infection, but their potential role during recovery and resolution of inflammation is unknown. We found that antibody-mediated CD86 blockade in vivo after virus clearance led to a delay in recovery, characterized by increased numbers of lung neutrophils and inflammatory cytokines in airways and lung interstitium, but no change in conventional IAV-specific T cell responses. However, CD86 blockade led to decreased numbers of FoxP3+ regulatory T cells (Tregs, and adoptive transfer of Tregs into αCD86 treated mice rescued the effect of the blockade, supporting a role for Tregs in promoting recovery after virus clearance. Specific depletion of Tregs late after infection mimicked the CD86 blockade phenotype, confirming a role for Tregs during recovery after virus clearance. Furthermore, we identified neutrophils as a target of Treg suppression since neutrophil depletion in Treg-depleted mice reduced excess inflammatory cytokines in the airways. These results demonstrate that Tregs, in a CD86 dependent mechanism, contribute to the resolution of disease after IAV infection, in part by suppressing neutrophil-driven cytokine release into the airways.

  14. Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4⁺ Foxp3⁺ regulatory T cells.

    Science.gov (United States)

    Hu, Ya; Xiao, Haitao; Shi, Tingchen; Oppenheim, Joost J; Chen, Xin

    2014-06-01

    Progranulin (PGRN) is a pleiotropic growth factor with immunosuppressive properties. Recently, it was reported that PGRN was an antagonist of tumour necrosis factor (TNF) receptors, preferentially for TNFR2. However, we and others showed that TNF-TNFR2 interaction was critical for the activation and expansion of functional CD4(+)  Foxp3(+) regulatory T (Treg) cells. We therefore examined the effect of PGRN on the proliferation of naturally occurring murine suppressive Treg cells induced by TNF. Consistent with our previous reports, TNF overcame the hyporesponsiveness of highly purified Treg cells to T-cell receptor stimulation. Furthermore, in the presence of interleukin-2, TNF preferentially stimulated proliferation of Treg cells contained in unfractionated CD4 cells. These effects of TNF on suppressive Treg cells were markedly increased by exogenous PGRN. TNF and TNFR2 interactions are required for this effect of PGRN, because the PGRN by itself did not stimulate Treg cell proliferation. The effect of PGRN on Treg cells was abrogated by antibody against TNFR2, and Treg cells deficient in TNFR2 also failed to respond to PGRN. Furthermore, PGRN also enhanced the proliferative responses of effector T cells to TNF, but to a lesser extent than that of Treg cells, presumably caused by the different levels of TNFR2 expression on these two subsets of CD4 cells. Hence, our data clearly show that PGRN promotes, rather than inhibits, the functional consequence of TNF-TNFR2 interaction on Treg cells. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  15. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Nirmala Chandralega Kampan

    2017-11-01

    Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

  16. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells.

    Science.gov (United States)

    Kampan, Nirmala Chandralega; Madondo, Mutsa Tatenda; McNally, Orla M; Stephens, Andrew N; Quinn, Michael A; Plebanski, Magdalena

    2017-01-01

    Epithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF). IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs. Ascites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2 + Tregs and TNFR2 - Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC. High levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4 + CD25 hi FoxP3 + Tregs, resulting in an increased TNFR2 + Treg/effector T cell ratio. Furthermore, TNFR2 + Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2 + Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2

  17. Deletion hotspots in AMACR promoter CpG island are cis-regulatory elements controlling the gene expression in the colon.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    2009-01-01

    Full Text Available Alpha-methylacyl-coenzyme A racemase (AMACR regulates peroxisomal beta-oxidation of phytol-derived, branched-chain fatty acids from red meat and dairy products -- suspected risk factors for colon carcinoma (CCa. AMACR was first found overexpressed in prostate cancer but not in benign glands and is now an established diagnostic marker for prostate cancer. Aberrant expression of AMACR was recently reported in Cca; however, little is known about how this gene is abnormally activated in cancer. By using a panel of immunostained-laser-capture-microdissected clinical samples comprising the entire colon adenoma-carcinoma sequence, we show that deregulation of AMACR during colon carcinogenesis involves two nonrandom events, resulting in the mutually exclusive existence of double-deletion at CG3 and CG10 and deletion of CG12-16 in a newly identified CpG island within the core promoter of AMACR. The double-deletion at CG3 and CG10 was found to be a somatic lesion. It existed in histologically normal colonic glands and tubular adenomas with low AMACR expression and was absent in villous adenomas and all CCas expressing variable levels of AMACR. In contrast, deletion of CG12-16 was shown to be a constitutional allele with a frequency of 43% in a general population. Its prevalence reached 89% in moderately differentiated CCas strongly expressing AMACR but only existed at 14% in poorly differentiated CCas expressing little or no AMACR. The DNA sequences housing these deletions were found to be putative cis-regulatory elements for Sp1 at CG3 and CG10, and ZNF202 at CG12-16. Chromatin immunoprecipitation, siRNA knockdown, gel shift assay, ectopic expression, and promoter analyses supported the regulation by Sp1 and ZNF202 of AMACR gene expression in an opposite manner. Our findings identified key in vivo events and novel transcription factors responsible for AMACR regulation in CCas and suggested these AMACR deletions may have diagnostic/prognostic value for

  18. Conflictual cooperation

    DEFF Research Database (Denmark)

    Axel, Erik

    2011-01-01

    This paper explores cooperation as contradictory and therefore with a constant possibility for conflict. Consequently it is called conflictual cooperation. The notion is presented on the basis of a participatory observation in a control room of a district heating system. In the investigation......, cooperation appeared as the continuous reworking of contradictions in the local arrangement of societal con- ditions. Subjects were distributed and distributed themselves according to social privileges, resources, and dilemmas in cooperation. Here, the subjects’ activities and understandings took form from...... on regulating who can use what in what way. Contradictions in the observed activity are discussed. It is argued that for the participants the connec- tions of acts appear in such contradictions in cooperation. This conception is dis- cussed in relationship to the notions of practice, as expounded by Bourdieu...

  19. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  20. Qualitative elements constituting effective agricultural cooperatives ...

    African Journals Online (AJOL)

    Agricultural cooperatives like all cooperatives are built on the principle of cooperation and community spirit, also known as ubuntu. They are widely promoted as a positive force for collective effort in smallholder agriculture development. However, research suggests that they generally have not been effective and successful ...

  1. 7 CFR 1220.107 - Cooperator organization.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Cooperator organization. 1220.107 Section 1220.107... CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.107 Cooperator organization. The term Cooperator Organization means the American Soybean Association, or any successor organization...

  2. Cooperative Learning in the Physical Education Classroom.

    Science.gov (United States)

    Dunn, Steven E.; Wilson, Rolayne

    1991-01-01

    Presents guidelines for promoting and using cooperative learning in physical education. To establish cooperative learning, teachers must plan for specific group dynamics. Physical educators need to understand their roles with groups and how groups should be structured. The article offers two cooperative learning lesson examples. (SM)

  3. 76 FR 34692 - Inside Passage Electric Cooperative

    Science.gov (United States)

    2011-06-14

    ... containing a single 600-kilowatt turbine/generator unit; (7) a small switchyard located adjacent to the... Energy Regulatory Commission Inside Passage Electric Cooperative Notice of Preliminary Permit Application..., 2011, and supplemented on May 18, 2011, the Inside Passage Electric Cooperative filed an application...

  4. Regulatory unbundling in telecommunications

    OpenAIRE

    Knieps, Günter

    2011-01-01

    Due to its dynamic nature, and the increasing importance of competitive sub-parts, the telecommunications sector provides particularly interesting insights for studying regulatory unbundling. Based on the theory of monopolistic bottle-necks the fallacies of overregulation by undue unbundling obligations are indicated. Neither the promotion of infrastructure competition by mandatory un-bundling of competitive subparts of telecommunications infrastructure, nor regulatory induced network fragmen...

  5. Thou should not know too much. When lack of information promotes co-operative behaviour. The case of oil-fields in Wyoming, Oklahoma and Texas

    Energy Technology Data Exchange (ETDEWEB)

    Hassler, B.

    1997-12-31

    Proper assumptions of information levels are of vital importance in all kinds of analysis of interdependent decision-making. In most cases the rule is; the more information the better. In this paper, however, it is shown that such is not always the case. Lack of information can enhance resource utilisation of resources, when the problem of co-operation is of a Prisoner`s dilemma type, and when iteration of the interaction game is unlikely. The case of oil-fields in the United States has been chosen as an empirical example of the latter. Optimal drilling procedures tend to be chosen more often the less the drillers know about the resource characteristics. This outcome is explained by the structure of the decision-making problem, where low levels of information render it advantageous to choose co-operative strategies 16 refs, 4 figs

  6. Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait.

    Science.gov (United States)

    Boyle, Kerry E; Monaco, Hilary; van Ditmarsch, Dave; Deforet, Maxime; Xavier, Joao B

    2015-05-01

    Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density dependent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable.

  7. Study on Banana Cooperatives in Hainan Province

    OpenAIRE

    HUANG, Huide; Zhang, Wanzhen; Liu, Enping; Zhang, Xizhu

    2013-01-01

    This paper gives an overview of the distribution, member scale, production and operation of banana cooperatives in Hainan Province, and points out the market risk and natural risk faced by the production of banana cooperatives in Hainan Province. In order to promote the banana cooperatives to form new agricultural management system integrating organization and intensification, this paper puts forth the production and operation recommendations, such as joint production of banana cooperatives, ...

  8. Promoting the Open Science culture in university libraries of developing countries: case studies of the French-speaking universities of Belgium cooperation programs in the Global South

    OpenAIRE

    Brodkom, Frédéric; Pochet, Bernard

    2017-01-01

    Watch the VIDEO here. Presenter - Frédéric Brodkom.The ARES-CCD (formerly CUD) is the French-speaking universities and high-school of Belgium Commission for the Cooperation to Development. With an annual budget of 31 M€ fully dedicated to the academic development of actually 19 universities of North and Central Africa, South-East Asia, Western South America and Greater Antilles, this commission brings together volunteers of the academic, scientific and administrative staffs of our universitie...

  9. TGF-β regulates the expression of transcription factor KLF6 and its splice variants and promotes co-operative transactivation of common target genes through a Smad3–Sp1–KLF6 interaction

    Science.gov (United States)

    BOTELLA, Luisa M.; SANZ-RODRIGUEZ, Francisco; KOMI, Yusuke; FERNANDEZ-L, Africa; VARELA, Elisa; GARRIDO-MARTIN, Eva M.; NARLA, Goutham; FRIEDMAN, Scott L.; KOJIMA, Soichi

    2010-01-01

    KLF6 (Krüppel-like factor 6) is a transcription factor and tumour suppressor with a growing range of biological activities and transcriptional targets. Among these, KLF6 suppresses growth through transactivation of TGF-β1 (transforming growth factor-β1). KLF6 can be alternatively spliced, generating lower-molecular-mass isoforms that antagonize the full-length WT (wild-type) protein and promote growth. A key target gene of full-length KLF6 is endoglin, which is induced in vascular injury. Endoglin, a homodimeric cell membrane glycoprotein and TGF-β auxiliary receptor, has a pro-angiogenic role in endothelial cells and is also involved in malignant progression. The aim of the present work was to explore the effect of TGF-β on KLF6 expression and splicing, and to define the contribution of TGF-β on promoters regulated by co-operation between KLF6 and Sp1 (specificity protein 1). Using co-transfection, co-immunoprecipitation and fluorescence resonance energy transfer, our data demonstrate that KLF6 co-operates with Sp1 in transcriptionally regulating KLF6-responsive genes and that this co-operation is further enhanced by TGF-β1 through at least two mechanisms. First, in specific cell types, TGF-β1 may decrease KLF6 alternative splicing, resulting in a net increase in full-length, growth-suppressive KLF6 activity. Secondly, KLF6–Sp1 co-operation is further enhanced by the TGF-β–Smad (similar to mothers against decapentaplegic) pathway via the likely formation of a tripartite KLF6–Sp1–Smad3 complex in which KLF6 interacts indirectly with Smad3 through Sp1, which may serve as a bridging molecule to co-ordinate this interaction. These findings unveil a finely tuned network of interactions between KLF6, Sp1 and TGF-β to regulate target genes. PMID:19076057

  10. Polymorphism in the regulatory region located more than 1.1 kilobases 5' to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, Steen; Morling, N

    1999-01-01

    in certain disorders of pregnancy. We have studied the DNA sequences of the putative regulatory region located more than 1.1 kilobases 5' from the start site of transcription (a 244 bp HindIII/EcoRI fragment) of the HLA-G gene and of the promoter region to detect any possible polymorphism. We detected one...... into two groups based on the detected polymorphism. The nucleotide substitutions may have implications for the binding of nuclear factors to the regulatory regions. To our knowledge this is the first study of any polymorphism in the 5'-flanking sequences to the HLA-G gene. Further studies are needed......The non-classic Human Leucocyte Antigen class Ib molecule, HLA-G, is expressed on the invasive, extra-villous cytotrophoblast in human placenta. HLA-G protects against natural killer (NK)-cell-mediated lysis and may modulate the secretion of cytokines. Aberrant expression of HLA-G has been reported...

  11. COOPERATION BETWEEN TEACHER AND PATIENTS

    Directory of Open Access Journals (Sweden)

    Egidija NOVLJAN

    1998-04-01

    Full Text Available The cooperation between the teacher and parents is very sensitive and significant field in context of promotion the development of the disabled children.With that in this article are elaborate many questions connected with successful communication between the teacher and parents. In the some time we have been engrossed in factors which made obstruct in communication, the tasks and the large register of the forms of cooperation in which are build in the huge experience come by former practice.

  12. The replication-independent histone H3-H4 chaperones HIR, ASF1, and RTT106 co-operate to maintain promoter fidelity.

    Science.gov (United States)

    Silva, Andrea C; Xu, Xiaomeng; Kim, Hyun-Soo; Fillingham, Jeffrey; Kislinger, Thomas; Mennella, Thomas A; Keogh, Michael-Christopher

    2012-01-13

    RNA polymerase II initiates from low complexity sequences so cells must reliably distinguish "real" from "cryptic" promoters and maintain fidelity to the former. Further, this must be performed under a range of conditions, including those found within inactive and highly transcribed regions. Here, we used genome-scale screening to identify those factors that regulate the use of a specific cryptic promoter and how this is influenced by the degree of transcription over the element. We show that promoter fidelity is most reliant on histone gene transactivators (Spt10, Spt21) and H3-H4 chaperones (Asf1, HIR complex) from the replication-independent deposition pathway. Mutations of Rtt106 that abrogate its interactions with H3-H4 or dsDNA permit extensive cryptic transcription comparable with replication-independent deposition factor deletions. We propose that nucleosome shielding is the primary means to maintain promoter fidelity, and histone replacement is most efficiently mediated in yeast cells by a HIR/Asf1/H3-H4/Rtt106 pathway.

  13. Une réaction à « Democracy Promotion at a Local Level : Experiences, Perspectives and Policy of Swiss International Cooperation » de Martin Dahinden

    Directory of Open Access Journals (Sweden)

    Olivier Roy

    2013-10-01

    Full Text Available L’article Democracy Promotion at a Local Level : Experiences, Perspectives and Policy of Swiss International Cooperation de Martin Dahinden présente une analyse fine et complexe de ce qui peut constituer une politique concrète et efficace d’aide à la démocratisation ; il en souligne les limites possibles, la complexité des niveaux d’intervention et la nécessité de la mettre en œuvre dans le cadre d’une société civile spécifique et d’enjeux de pouvoir locaux.Cette aide à la démocratisation s’i...

  14. Predicting Human Cooperation.

    Directory of Open Access Journals (Sweden)

    John J Nay

    Full Text Available The Prisoner's Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner's Dilemma (defection, when played by both players, is mutually harmful. Repetition of the Prisoner's Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner's Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner's Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. We demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation.

  15. Vascular injury triggers Krüppel-like factor 6 mobilization and cooperation with specificity protein 1 to promote endothelial activation through upregulation of the activin receptor-like kinase 1 gene.

    Science.gov (United States)

    Garrido-Martín, Eva M; Blanco, Francisco J; Roquè, Mercé; Novensà, Laura; Tarocchi, Mirko; Lang, Ursula E; Suzuki, Toru; Friedman, Scott L; Botella, Luisa M; Bernabéu, Carmelo

    2013-01-04

    Activin receptor-like kinase-1 (ALK1) is an endothelial transforming growth factor β receptor involved in angiogenesis. ALK1 expression is high in the embryo vasculature, becoming less detectable in the quiescent endothelium of adult stages. However, ALK1 expression becomes rapidly increased after angiogenic stimuli such as vascular injury. To characterize the molecular mechanisms underlying the regulation of ALK1 on vascular injury. Alk1 becomes strongly upregulated in endothelial (EC) and vascular smooth muscle cells of mouse femoral arteries after wire-induced endothelial denudation. In vitro denudation of monolayers of human umbilical vein ECs also leads to an increase in ALK1. Interestingly, a key factor in tissue remodeling, Krüppel-like factor 6 (KLF6) translocates to the cell nucleus during wound healing, concomitantly with an increase in the ALK1 gene transcriptional rate. KLF6 knock down in human umbilical vein ECs promotes ALK1 mRNA downregulation. Moreover, Klf6(+/-) mice have lower levels of Alk1 in their vasculature compared with their wild-type siblings. Chromatin immunoprecipitation assays show that KLF6 interacts with ALK1 promoter in ECs, and this interaction is enhanced during wound healing. We demonstrate that KLF6 is transactivating ALK1 gene, and this transactivation occurs by a synergistic cooperative mechanism with specificity protein 1. Finally, Alk1 levels in vascular smooth muscle cells are not directly upregulated in response to damage, but in response to soluble factors, such as interleukin 6, released from ECs after injury. ALK1 is upregulated in ECs during vascular injury by a synergistic cooperative mechanism between KLF6 and specificity protein 1, and in vascular smooth muscle cells by an EC-vascular smooth muscle cell paracrine communication during vascular remodeling.

  16. Vascular Injury Triggers Krüppel-Like Factor 6 (KLF6) Mobilization and Cooperation with Sp1 to Promote Endothelial Activation through Upregulation of the Activin Receptor-Like Kinase 1 (ALK1) Gene

    Science.gov (United States)

    Garrido-Martín, Eva M.; Blanco, Francisco J.; Roquè, Mercé; Novensà, Laura; Tarocchi, Mirko; Lee, Ursula E.; Suzuki, Toru; Friedman, Scott L.; Botella, Luisa M.; Bernabéu, Carmelo

    2012-01-01

    Rationale Activin receptor-Like Kinase-1 (ALK1) is an endothelial TGF-β receptor involved in angiogenesis. ALK1 expression is high in the embryo vasculature, becoming less detectable in the quiescent endothelium of adult stages. However, ALK1 expression becomes rapidly increased after angiogenic stimuli such as vascular injury. Objective To characterize the molecular mechanisms underlying the regulation of ALK1 upon vascular injury. Methods and Results Alk1 becomes strongly upregulated in endothelial (EC) and vascular smooth muscle cells (vSMC) of mouse femoral arteries after wire-induced endothelial denudation. In vitro, denudation of monolayers of Human Umbilical Vein Endothelial Cells (HUVEC) also leads to an increase in ALK1. Interestingly, a key factor in tissue remodeling, Krüppel-like factor 6 (KLF6), translocates to the cell nucleus during wound healing, concomitantly with an increase in the ALK1 gene transcriptional rate. KLF6 knock down in HUVECs promotes ALK1 mRNA downregulation. Moreover, Klf6+/− mice have lower levels of Alk1 in their vasculature compared with their wild type siblings. Chromatin immunoprecipitation assays show that KLF6 interacts with ALK1 promoter in ECs, and this interaction is enhanced during wound healing. We demonstrate that KLF6 is transactivating ALK1 gene, and this transactivation occurs by a synergistic cooperative mechanism with Sp1. Finally, Alk1 levels in vSMCs are not directly upregulated in response to damage, but in response to soluble factors, such as IL-6, released from ECs after injury. Conclusions ALK1 is upregulated in ECs during vascular injury by a synergistic cooperative mechanism between KLF6 and Sp1, and in vSMCs by an EC-vSMC paracrine communication during vascular remodeling. PMID:23048070

  17. The US-Nigerian Military Cooperation: US Africom As A Mentor For Nigeria’s Military Efforts At Promoting Respect For Human Rights

    Science.gov (United States)

    2016-06-01

    human nature.1 In the same vein, the universality of human rights was affirmed in the adoption of the Universal Declaration of Human Rights (UDHR) by...A MENTOR FOR NIGERIA’S MILITARY EFFORTS AT PROMOTING RESPECT FOR HUMAN RIGHTS By Mohammed Asuekome Imam, Major, Nigerian Air Force BSc... rights abuses. The effort Nigerian military leadership at stemming this trend has not yielded the desired outcome, and human

  18. GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis.

    Science.gov (United States)

    Maric, G; Annis, M G; Dong, Z; Rose, A A N; Ng, S; Perkins, D; MacDonald, P A; Ouellet, V; Russo, C; Siegel, P M

    2015-10-01

    Glycoprotein nmb (GPNMB) promotes breast tumor growth and metastasis and its expression in tumor epithelium correlates with poor prognosis in breast cancer patients. Despite its biological and clinical significance, little is known regarding the molecular mechanisms engaged by GPNMB. Herein, we show that GPNMB engages distinct functional domains and mechanisms to promote primary tumor growth and metastasis. We demonstrate that neuropilin-1 (NRP-1) expression is increased in breast cancer cells that overexpress GPNMB. Interestingly, the GPNMB-driven increase in NRP-1 expression potentiated vascular endothelial growth factor signaling in breast cancer cells and was required for the growth, but not metastasis, of these cells in vivo. Interrogation of RNAseq data sets revealed a positive correlation between GPNMB and NRP-1 levels in human breast tumors. Furthermore, we ascribe pro-growth and pro-metastatic functions of GPNMB to its ability to bind α5β1 integrin and increase downstream signaling in breast cancer cells. We show that GPNMB enhances breast cancer cell adhesion to fibronectin, increases α5β1 expression and associates with this receptor through its RGD motif. GPNMB recruitment into integrin complexes activates Src and Fak signaling pathways in an RGD-dependent manner. Importantly, both the RGD motif and cytoplasmic tail of GPNMB are required to promote primary mammary tumor growth; however, only mutation of the RGD motif impaired the formation of lung metastases. Together, these findings identify novel and distinct molecular mediators of GPNMB-induced breast cancer growth and metastasis.

  19. Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function

    Directory of Open Access Journals (Sweden)

    Alexandre Bignon

    2017-05-01

    Full Text Available Treatments to limit T cell activation are essential for managing autoimmune and inflammatory disorders. The B subunit of Escherichia coli heat-labile enterotoxin (EtxB is known to ameliorate inflammatory disease in vivo but the mechanism by which this is mediated is not well understood. Here, we show that following intranasal administration, EtxB acts on two key cellular regulators of T cell activation: regulatory T cells and dendritic cells (DCs. EtxB enhances the proliferation of lung regulatory T cells and doubles their suppressive function, likely through an increase in expression of the Treg effector molecule CTLA-4. EtxB supports the generation of interleukin-10-producing DCs that are unable to activate T cells. These data show, for the first time, that mucosal EtxB treatment limits T cells activation by acting jointly on two distinct types of immune cells.

  20. Social setting, intuition and experience in laboratory experiments interact to shape cooperative decision-making

    National Research Council Canada - National Science Library

    Capraro, Valerio; Cococcioni, Giorgia

    2015-01-01

    ...: promoting intuition versus deliberation typically has a positive effect on cooperation (dynamism) among people living in a cooperative setting and with no previous experience in economic games on cooperation...

  1. 75 FR 15704 - Old Dominion Electric Cooperative; North Carolina Electric Membership Corporation, Complainants v...

    Science.gov (United States)

    2010-03-30

    ... Energy Regulatory Commission Old Dominion Electric Cooperative; North Carolina Electric Membership Corporation, Complainants v. Virginia Electric and Power Company, Respondent; Notice of Complaint March 23...), Old Dominion Electric Cooperative and North Carolina Electric Membership Corporation (Complainants...

  2. Cooperative design

    DEFF Research Database (Denmark)

    Schmidt, Kjeld

    1998-01-01

    In the contemporary world, engineers and designers face huge challenges as they shift towards novel organizational concepts such as ‘concurrent engineering’ in order to manage increasing product diversity so as to satisfy customer demands while trying to accelerate the design process to deal...... with the competitive realities of a global market and decreasing product life cycles. In this environment, the coordination and integration of the myriads of interdependent and yet distributed and concurrent design activities becomes enormously complex. It thus seems as if CSCW technologies may be indispensable...... if concurrent engineering is to succeed. On the basis of ethnographic studies of cooperative design, the paper attempts to characterize cooperative work in the domain of design and to outline a set of crucial research problems to be addressed if CSCW is to help engineers and de-signers meet the challenges...

  3. FUNCIÓN DE LAS COOPERATIVAS EN LA NORMATIVA DE FOMENTO DEL DESARROLLO RURAL/FUNCTION OF THE CO-OPERATIVES IN THE REGULATION OF THE RURAL DEVELOPMENT PROMOTION

    Directory of Open Access Journals (Sweden)

    Luis GALLEGO SEVILLA

    2007-05-01

    the European Agricultural Fund for Rural Development (EAFRD. The member States’ legislation applies and implements the European rules, but it develops, in addition, local regulations about cooperatives and rural development. In the Spanish case, national and regional legislation about both cooperatives and rural development has to be taken into account. In this paper, the role that agrarian cooperatives fulfil on rural development within the EU, national and regional legal frameworks is analyzed, based on the substantive Spanish legislation. Agrarian cooperatives are local development promoting agents as a intermediary with the public administrations, and as members of the “local action groups” set up by the LEADER methodology. Likewise, agrarian cooperatives may be recipient of additional aids that several Spanish Autonomous Communities provide to carry out local development measures.

  4. [Social cooperatives in Italy].

    Science.gov (United States)

    Villotti, P; Zaniboni, S; Fraccaroli, F

    2014-06-01

    This paper describes the role of social cooperatives in Italy as a type of economic, non-profit organization and their role in contributing to the economic and social growth of the country. The purpose of this paper is to learn more about the experience of the Italian social cooperatives in promoting the work integration process of disadvantaged workers, especially those suffering from mental disorders, from a theoretical and an empirical point of view. Social enterprise is the most popular and consolidated legal and organizational model for social enterprises in Italy, introduced by Law 381/91. Developed during the early 1980s, and formally recognized by law in the early 1990s, social cooperatives aim at pursuing the general interest of the community to promote the human needs and social inclusion of citizens. They are orientated towards aims that go beyond the interest of the business owners, the primary beneficiary of their activities is the community, or groups of disadvantaged people. In Italy, Law 381/91 distinguishes between two categories of social cooperatives, those producing goods of social utility, such as culture, welfare and educational services (A-type), and those providing economic activities for the integration of disadvantaged people into employment (B-type). The main purpose of B-type social cooperatives is to integrate disadvantaged people into the open labour market. This goal is reached after a period of training and working experience inside the firm, during which the staff works to improve both the social and professional abilities of disadvantaged people. During the years, B-type social co-ops acquired a particular relevance in the care of people with mental disorders by offering them with job opportunities. Having a job is central in the recovery process of people suffering from mental diseases, meaning that B-type social co-ops in Italy play an important rehabilitative and integrative role for this vulnerable population of workers. The

  5. Nuclear safety assessment of nuclear power plants and nuclear risk in Eastern Europe and other regions. Scientific-technical cooperation with nuclear regulatory authorities and technical support organizations (TSOs); Einschaetzung der nuklearen Sicherheit von Kernkraftwerken sowie nuklearer Risiken in Osteuropa und anderen Regionen. Wissenschaftlich-technische Zusammenarbeit mit atomrechtlichen Behoerden und deren Sachverstaendigenorganisationen (TSO)

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Holger

    2014-09-15

    The BMUB/BfS project 3611I01512 formed the frame of the GRS for the scientifictechnical cooperation with Technical Support Organisations and Nuclear Regulatory Authorities in the field of nuclear safety of NPPs and for the evaluation of nuclear risks in Eastern Europe and other regions for the period from September 2011 till June 2014. In the present final report main results of the project are described. The project comprised the following technical topics: - Record status of NPP modernisation programs, Monitoring and evaluation of modernisation programs; - Design basis and severe accident analyses for NPP with PWR (WWER-440, WWER-1000); - Cooperation with INSC partner countries on DBA, BDBA and severe accident analyses for WWER plants of generation 3+ and on building NRA and safety evaluation capacities; - Decommissioning of nuclear facilities and disposal of radioactive waste; - Evaluation of new reactor concepts and their safety design; Panels at regulatory level. The work results are preceded by a summary on the activities related to the project management and to the planning of the bilateral work.

  6. Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients.

    Science.gov (United States)

    Haschemi Nassab, Mani; Rhein, Mathias; Hagemeier, Lars; Kaeser, Marius; Muschler, Marc; Glahn, Alexander; Pich, Andreas; Heberlein, Annemarie; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas

    2016-01-01

    Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort. © 2015 S. Karger AG, Basel.

  7. The PLZF-like protein TRA-4 cooperates with the Gli-like transcription factor TRA-1 to promote female development in C. elegans.

    Science.gov (United States)

    Grote, Phillip; Conradt, Barbara

    2006-10-01

    The Gli-like transcription factor TRA-1 of C. elegans promotes female development by repressing the transcription of male-specific genes. We have found that tra-1 interacts with tra-4, a previously uncharacterized gene that encodes a protein similar to the human proto-oncoprotein and transcriptional repressor PLZF. In this context, the TRA-4 protein functions with NASP-1, a C. elegans homolog of the mammalian histone chaperone NASP, and the histone deacetylase HDA-1. We also found that tra-4 is a member of the synMuv B group of genes, many of which encode homologs of components of the Drosophila Myb-Muv B transcriptional repressor complex, and that several synMuv B genes also promote female development. Based on these results, we propose that male-specific genes are repressed in C. elegans hermaphrodites by the combined action of TRA-1/Gli, a complex composed of TRA-4/PLZF-like, NASP, and HDA-1/HDAC, and synMuv B proteins. Similar interactions may function in sex determination and developmental regulation in other species.

  8. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  9. Let's Cooperate! Integrating Cooperative Learning Into a Lesson on Ethics.

    Science.gov (United States)

    Reineke, Patricia R

    2017-04-01

    Cooperative learning is an effective teaching strategy that promotes active participation in learning and can be used in academic, clinical practice, and professional development settings. This article describes that strategy and provides an example of its use in a lesson about ethics. J Contin Nurs Educ. 2017;48(4):154-156. Copyright 2017, SLACK Incorporated.

  10. The population genetics of cooperative gene regulation

    Directory of Open Access Journals (Sweden)

    Stewart Alexander J

    2012-09-01

    Full Text Available Abstract Background Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. Rewiring of transcriptional networks is achieved either by changes to transcription factor binding sites or by changes to the physical interactions among transcription factor proteins. It has been suggested that the evolution of cooperative binding among factors can facilitate the adaptive rewiring of a regulatory network. Results We use a population-genetic model to explore when cooperative binding of transcription factors is favored by evolution, and what effects cooperativity then has on the adaptive re-writing of regulatory networks. We consider a pair of transcription factors that regulate multiple targets and overlap in the sets of target genes they regulate. We show that, under stabilising selection, cooperative binding between the transcription factors is favoured provided the amount of overlap between their target genes exceeds a threshold. The value of this threshold depends on several population-genetic factors: strength of selection on binding sites, cost of pleiotropy associated with protein-protein interactions, rates of mutation and population size. Once it is established, we find that cooperative binding of transcription factors significantly accelerates the adaptive rewiring of transcriptional networks under positive selection. We compare our qualitative predictions to systematic data on Saccharomyces cerevisiae transcription factors, their binding sites, and their protein-protein interactions. Conclusions Our study reveals a rich set of evolutionary dynamics driven by a tradeoff between the beneficial effects of cooperative binding at targets shared by a pair of factors, and the detrimental effects of cooperative binding for non-shared targets. We find that cooperative regulation will evolve when transcription factors share a sufficient proportion of their target genes. These findings help to

  11. The Long Way Toward Cooperation

    Directory of Open Access Journals (Sweden)

    Thomas Foth

    2015-01-01

    Full Text Available To better understand why cooperation between health care professionals is still often problematic, we carried out 25 semistructured face-to-face expert interviews with physicians and nurses in different rural and urban areas in northern Germany. Using Mayring’s qualitative content analysis method to analyze the data collected, we found that doctors and nurses interpreted interprofessional conflicts differently. Nursing seems to be caught in a paradoxical situation: An increasing emphasis is placed on achieving interprofessional cooperation but the core areas of nursing practice are subject to increasing rationalization in the current climate of health care marketization. The subsequent and systematic devaluation of nursing work makes it difficult for physicians to acknowledge nurses’ expertise. We suggest that to ameliorate interprofessional cooperation, nursing must insist on its own logic of action thereby promoting its professionalization; interprofessional cooperation cannot take place until nursing work is valued by all members of the health care system.

  12. A cooperative interaction between nontranslated RNA sequences and NS5A protein promotes in vivo fitness of a chimeric hepatitis C/GB virus B.

    Directory of Open Access Journals (Sweden)

    Lucile Warter

    Full Text Available GB virus B (GBV-B is closely related to hepatitis C virus (HCV, infects small non-human primates, and is thus a valuable surrogate for studying HCV. Despite significant differences, the 5' nontranslated RNAs (NTRs of these viruses fold into four similar structured domains (I-IV, with domains II-III-IV comprising the viral internal ribosomal entry site (IRES. We previously reported the in vivo rescue of a chimeric GBV-B (vGB/III(HC containing HCV sequence in domain III, an essential segment of the IRES. We show here that three mutations identified within the vGB/III(HC genome (within the 3'NTR, upstream of the poly(U tract, and NS5A coding sequence are necessary and sufficient for production of this chimeric virus following intrahepatic inoculation of synthetic RNA in tamarins, and thus apparently compensate for the presence of HCV sequence in domain III. To assess the mechanism(s underlying these compensatory mutations, and to determine whether 5'NTR subdomains participating in genome replication do so in a virus-specific fashion, we constructed and evaluated a series of chimeric subgenomic GBV-B replicons in which various 5'NTR subdomains were substituted with their HCV homologs. Domains I and II of the GBV-B 5'NTR could not be replaced with HCV sequence, indicating that they contain essential, virus-specific RNA replication elements. In contrast, domain III could be swapped with minimal loss of genome replication capacity in cell culture. The 3'NTR and NS5A mutations required for rescue of the related chimeric virus in vivo had no effect on replication of the subgenomic GBneoD/III(HC RNA in vitro. The data suggest that in vivo fitness of the domain III chimeric virus is dependent on a cooperative interaction between the 5'NTR, 3'NTR and NS5A at a step in the viral life cycle subsequent to genome replication, most likely during particle assembly. Such a mechanism may be common to all hepaciviruses.

  13. Cooperative Learning Principles Enhance Online Interaction

    Science.gov (United States)

    Jacobs, George; Seow, Peter

    2014-01-01

    This paper describes eight principles that can be used to promote cooperative interactions among students working in online environments. The principles derive from a well-established approach to education, known variously as cooperative learning and collaborative learning. Each principle is explained as to what it means, why it is important and…

  14. Structuring Cooperative Group Work in Classrooms

    Science.gov (United States)

    Gillies, Robyn M.

    2003-01-01

    Cooperative, small-group learning is widely recognised as a pedagogical practice that promotes learning and socialisation across a range of curriculum areas from primary school through to high school and college. When children work cooperatively together, they learn to give and receive help, share their ideas and listen to other students'…

  15. A 5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle.

    Directory of Open Access Journals (Sweden)

    Yong-Zhen Huang

    Full Text Available Zinc finger, BED-type containing 6 (ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. Polymorphisms in its promoter and coding regions are likely to impact ZBED6 transcription and growth traits. In this study, rapid amplification of 5' cDNA ends (5'-RACE analysis revealed two transcription start sites (TSS for the bovine ZBED6 starting within exon 1 of the ZC3H11A gene (TSS-1 and upstream of the translation start codon of the ZBED6 gene (TSS-2. There was one SNP in the promoter and two missense mutations in the coding region of the bovine ZBED6 by sequencing of the pooled DNA samples (Pool-Seq, n = 100. The promoter and coding region are the key regions for gene function; polymorphisms in these regions can alter gene expression. Quantitative real-time PCR (qPCR analysis showed that ZBED6 has a broad tissue distribution in cattle and is highly expressed in skeletal muscle. Eleven promoter-detection vectors were constructed, which enabled the cloning of putative promoter sequences and analysis of ZBED6 transcriptional activity by luciferase reporter gene assays. The core region of the basal promoter of bovine ZBED6 is located within region -866 to -556. The activity of WT-826G-pGL3 in driving reporter gene transcription is significantly higher than that of the M-826A-pGL3 construct (P < 0.01. Analysis of gene expression patterns in homozygous full-sibling Chinese Qinchuan cattle showed that the mutant-type Hap-AGG exhibited a lower mRNA level than the wild-type Hap-GCA (P < 0.05 in longissimus dorsi muscle (LDM. Moreover, ZBED6 mRNA expression was low in C2C12 cells overexpressing the mutant-type ZBED6 (pcDNA3.1(+-Hap-GG (P < 0.01. Our results suggest that the polymorphisms in the promoter and coding regions may modulate the promoter activity and gene expression of bovine ZBED6 in the skeletal muscles of these cattle breeds.

  16. Cooperative learning: Review of research and practice

    National Research Council Canada - National Science Library

    Gillies, Robyn M

    2016-01-01

    Cooperative learning is widely recognised as a pedagogical practice that promotes socialization and learning among students from pre-school through to tertiary level and across different subject domains...

  17. Social Evolution: When Promiscuity Breeds Cooperation

    OpenAIRE

    van Zweden, Jelle S.; Cardoen, Dries; Wenseleers, Tom

    2012-01-01

    In social evolution theory, it has become common wisdom that close family ties should promote cooperative behaviour. Yet, in social insects, evidence is accumulating that queen promiscuity and low relatedness sometimes work better.

  18. The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling.

    Science.gov (United States)

    Eucker, Tyson P; Konkel, Michael E

    2012-02-01

    This study was performed to elucidate the host cell scaffolding and signalling molecules that Campylobacter jejuni utilizes to invade epithelial cells. We hypothesized that the C. jejuni fibronectin-binding proteins and secreted proteins are required for cell signalling and maximal invasion of host cells. C. jejuni binding to host cells via the CadF and FlpA fibronectin-binding proteins activated the epidermal growth factor (EGF) pathway, as evidenced by inhibitor studies and immunoprecipitation coupled with immunoblot analysis using antibodies reactive against total and active EGF receptor. Inhibitor studies revealed maximal C. jejuni host cell invasion was dependent upon PI3-Kinase, c-Src and focal adhesion kinase (FAK), all of which are known to participate in cytoskeletal rearrangements. Knockdown of endogenous Dock180, which is a Rac1-specific guanine nucleotide exchange factor, using siRNA revealed that C. jejuni invasion was significantly reduced compared with cells treated with scrambled siRNA. We further demonstrated that the C. jejuni Cia proteins are, in part, responsible for Rho GTPase Rac1 recruitment and activation, as judged by immunofluorescence microscopy and Rac1 activation. Based on these data, we present a model that illustrates that C. jejuni utilizes a coordinated mechanism involving both adhesins and secreted proteins to promote membrane ruffling and host cell invasion. © 2011 Blackwell Publishing Ltd.

  19. Differential acetylation of histone H3 at the regulatory region of OsDREB1b promoter facilitates chromatin remodelling and transcription activation during cold stress.

    Directory of Open Access Journals (Sweden)

    Dipan Roy

    Full Text Available The rice ortholog of DREB1, OsDREB1b, is transcriptionally induced by cold stress and over-expression of OsDREB1b results in increase tolerance towards high salt and freezing stress. This spatio-temporal expression of OsDREB1b is preceded by the change in chromatin structure at the promoter and the upstream region for gene activation. The promoter and the upstream region of OsDREB1b genes appear to be arranged into a nucleosome array. Nucleosome mapping of ∼ 700 bp upstream region of OsDREB1b shows two positioned nucleosomes between -610 to -258 and a weakly positioned nucleosome at the core promoter and the TSS. Upon cold stress, there is a significant change in the nucleosome arrangement at the upstream region with increase in DNaseI hypersensitivity or MNase digestion in the vicinity of cis elements and TATA box at the core promoter. ChIP assays shows hyper-acetylation of histone H3K9 throughout the locus whereas region specific increase was observed in H3K14ac and H3K27ac. Moreover, there is an enrichment of RNA PolII occupancy at the promoter region during transcription activation. There is no significant change in the H3 occupancy in OsDREB1b locus negating the possibility of nucleosome loss during cold stress. Interestingly, cold induced enhanced transcript level of OsDREB1b as well as histone H3 acetylation at the upstream region was found to diminish when stressed plants were returned to normal temperature. The result indicates absolute necessity of changes in chromatin conformation for the transcription up-regulation of OsDREB1b gene in response to cold stress. The combined results show the existence of closed chromatin conformation at the upstream and promoter region of OsDREB1b in the transcription "off" state. During cold stress, changes in region specific histone modification marks promote the alteration of chromatin structure to facilitate the binding of transcription machinery for proper gene expression.

  20. CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.

    Science.gov (United States)

    Xia, Mingcan; Hu, Shaomin; Fu, Yaoyao; Jin, Wensen; Yi, Qiyi; Matsui, Yurika; Yang, Jie; McDowell, Mary Ann; Sarkar, Surojit; Kalia, Vandana; Xiong, Na

    2014-09-01

    CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation. Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin. CCR10 is a critical regulator of skin immune homeostasis. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. The arbuscular mycorrhizal symbiosis promotes the systemic induction of regulatory defence-related genes in rice leaves and confers resistance to pathogen infection.

    Science.gov (United States)

    Campos-Soriano, Lidia; García-Martínez, José; San Segundo, Blanca

    2012-08-01

    Arbuscular mycorrhizal (AM) symbioses are mutualistic associations between soil fungi and most vascular plants. Their association benefits the host plant by improving nutrition, mainly phosphorus nutrition, and by providing increased capability to cope with adverse conditions. In this study, we investigated the transcriptional changes triggered in rice leaves as a result of AM symbiosis, focusing on the relevance of the plant defence response. We showed that root colonization by the AM fungus Glomus intraradices is accompanied by the systemic induction of genes that play a regulatory role in the host defence response, such as OsNPR1, OsAP2, OsEREBP and OsJAmyb. Genes involved in signal transduction processes (OsDUF26 and OsMPK6) and genes that function in calcium-mediated signalling processes (OsCBP, OsCaM and OsCML4) are also up-regulated in leaves of mycorrhizal rice plants in the absence of pathogen infection. In addition, the mycorrhizal rice plants exhibit a stronger induction of defence marker genes [i.e. pathogenesis-related (PR) genes] in their leaves in response to infection by the blast fungus Magnaporthe oryzae. Evidence indicates that mycorrhizal rice plants show enhanced resistance to the rice blast fungus. Overall, these results suggest that the protective effect of the AM symbiosis in rice plants relies on both the systemic activation of defence regulatory genes in the absence of pathogen challenge and the priming for stronger expression of defence effector genes during pathogen infection. The possible mechanisms involved in the mycorrhiza-induced resistance to M. oryzae infection are discussed. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

  2. Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states.

    Science.gov (United States)

    Preston, Charles; Chahal, Harinder S; Porrás, Analia; Cargill, Lucette; Hinds, Maryam; Olowokure, Babatunde; Cummings, Rudolph; Hospedales, James

    2016-05-01

    Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. "Regionalization"-an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems-may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative's concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

  3. Health promotion is peace promotion.

    Science.gov (United States)

    Middleton, J D

    1987-01-01

    This paper discusses the effects of the arms race on health, in the absence of nuclear war. High levels of military expenditure are inextricably linked to unemployment, poverty, starvation and ill health. Alternatives to the escalation of military expenditure are possible; health promotion can be involved in wider public health initiatives towards economic and industrial conversion to peaceful, socially useful production. The interests of the health and scientific communities have traditionally transcended narrow chauvinism and nationalism. World Health Organization activities such as work towards primary health care and the Expanded Programme on Immunization actively involve international co-operation, demystify potential enemies and promote health and peace.

  4. Parochial trust and cooperation across 17 societies.

    Science.gov (United States)

    Romano, Angelo; Balliet, Daniel; Yamagishi, Toshio; Liu, James H

    2017-11-28

    International challenges such as climate change, poverty, and intergroup conflict require countries to cooperate to solve these complex problems. However, the political tide in many countries has shifted inward, with skepticism and reluctance to cooperate with other countries. Thus, cross-societal investigations are needed to test theory about trust and cooperation within and between groups. We conducted an experimental study in 17 countries designed to test several theories that explain why, who, and where people trust and cooperate more with ingroup members, compared with outgroup members. The experiment involved several interactions in the trust game, either as a trustor or trustee. We manipulated partner group membership in the trust game (ingroup, outgroup, or unknown) and if their reputation was at stake during the interaction. In addition to the standard finding that participants trust and cooperate more with ingroup than outgroup members, we obtained findings that reputational concerns play a decisive role for promoting trust and cooperation universally across societies. Furthermore, men discriminated more in favor of their ingroup than women. Individual differences in cooperative preferences, as measured by social value orientation, predicted cooperation with both ingroup and outgroup members. Finally, we did not find support for three theories about the cross-societal conditions that influence the degree of ingroup favoritism observed across societies (e.g., material security, religiosity, and pathogen stress). We discuss the implications for promoting cooperation within and between countries. Copyright © 2017 the Author(s). Published by PNAS.

  5. T Regulatory Cell Induced Foxp3 Binds the IL2, IFNγ, and TNFα Promoters in Virus-Specific CD8+ T Cells from Feline Immunodeficiency Virus Infected Cats.

    Science.gov (United States)

    Wang, Yan; Nag, Mukta; Tuohy, Joanne L; De Paris, Kristina; Fogle, Jonathan E

    2017-11-17

    Polyfunctional CD8+ T cells play a critical role in controlling viremia during AIDS lentiviral infections. However, for most HIV-infected individuals, virus-specific CD8+ T cells exhibit loss of polyfunctionality, including loss of IL2, TNFα, and IFNγ. Using the feline immunodeficiency virus (FIV) model for AIDS lentiviral persistence, our laboratory has demonstrated that FIV-activated Treg cells target CD8+ T cells, leading to a reduction in IL2 and IFNγ production. Furthermore, we have demonstrated that Treg cells induce expression of the repressive transcription factor, Foxp3, in CD8+ T cells. Based upon these findings, we asked if Treg-induced Foxp3 could bind to the IL2, TNFα, and IFNγ promoter regions in virus-specific CD8+ T cells. Following coculture with autologous Treg cells, we demonstrated decreased mRNA levels of IL2 and IFNγ at weeks 4 and 8 postinfection and decreased TNFα at week 4 postinfection in virus-specific CD8+ T cells. We also clearly demonstrated Treg cell-induced Foxp3 expression in virus-specific CD8+ T cells at weeks 1, 4, and 8 postinfection. Finally, we documented Foxp3 binding to the IL2, TNFα, and IFNγ promoters at 8 weeks and 6 months postinfection in virus-specific CD8+ T cells following Treg cell coculture. In summary, the results here clearly demonstrate that Foxp3 inhibits IL2, TNFα, and IFNγ transcription by binding to their promoter regions in lentivirus-specific CD8+ T cells. We believe this is the first description of this process during the course of AIDS lentiviral infection.

  6. An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function.

    Science.gov (United States)

    Oh, Hyunju; Grinberg-Bleyer, Yenkel; Liao, Will; Maloney, Dillon; Wang, Pingzhang; Wu, Zikai; Wang, Jiguang; Bhatt, Dev M; Heise, Nicole; Schmid, Roland M; Hayden, Matthew S; Klein, Ulf; Rabadan, Raul; Ghosh, Sankar

    2017-09-19

    Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles. c-Rel was critical for thymic Treg development while p65 was essential for mature Treg identity and maintenance of immune tolerance. Transcriptome and NF-κB p65 binding analyses demonstrated a lineage specific, NF-κB-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-κB in Tconv and Treg cells highlight the functional plasticity of the NF-κB signaling pathway and underscores the need for more selective strategies to therapeutically target NF-κB. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Role of Cooperatives in Small and Medium Scale Enterprises (SMEs ...

    African Journals Online (AJOL)

    Reform of the cooperative policy framework, including legal and regulatory procedures is desirable. Other areas needing attention are capacity building to address the problems associated with management and leadership skills in the societies and the need to strengthen the cooperative governance system. Key words: ...

  8. A unified architecture of transcriptional regulatory elements

    DEFF Research Database (Denmark)

    Andersson, Robin; Sandelin, Albin Gustav; Danko, Charles G.

    2015-01-01

    Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However...... and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements....

  9. Fiscal 1996 research cooperation promotion project. Report on the Japan/Mexico international cooperation research on recovery of valuable elements in brine; 1996 nendo kenkyu kyoryoku suishin jigyo. Kansuichu no yuka shigen kaishu gijutsu ni kansuru kenkyu kyoryoku follow up hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    In the research cooperation promotion projects having been carried out, the R and D of an overall recovery system have been conducted which recovers effectively and systematically valuable resources such as magnesium, bromine and boron including in brine made after the salt manufacturing in the coastal region in Mexico. In this project, as the research on the distilling process needed for commercialization of the system to recover valuable resources from the brine, Japan has been collecting information on various distilling processes and solar pond systems and studying a distilling process appropriate to the site jointly with Mexico. As a result, a seawater desalination process which combined the solar pond using solar energy and the evaporation method was recommended as a low-priced distilling method. Moreover, it was indicated that the solar still method for condensing/recovering the evaporated water of the Guerrero Negro salt pan is also less influential in the salt manufacturing process and is viable as a most economical distilling process by studying the structural design and operational method of more efficient solar stills

  10. Third-party punishment increases cooperation in children through (misaligned) expectations and conditional cooperation.

    Science.gov (United States)

    Lergetporer, Philipp; Angerer, Silvia; Glätzle-Rützler, Daniela; Sutter, Matthias

    2014-05-13

    The human ability to establish cooperation, even in large groups of genetically unrelated strangers, depends upon the enforcement of cooperation norms. Third-party punishment is one important factor to explain high levels of cooperation among humans, although it is still somewhat disputed whether other animal species also use this mechanism for promoting cooperation. We study the effectiveness of third-party punishment to increase children's cooperative behavior in a large-scale cooperation game. Based on an experiment with 1,120 children, aged 7 to 11 y, we find that the threat of third-party punishment more than doubles cooperation rates, despite the fact that children are rarely willing to execute costly punishment. We can show that the higher cooperation levels with third-party punishment are driven by two components. First, cooperation is a rational (expected payoff-maximizing) response to incorrect beliefs about the punishment behavior of third parties. Second, cooperation is a conditionally cooperative reaction to correct beliefs that third party punishment will increase a partner's level of cooperation.

  11. Promotion of Autoimmune Diabetes by Cereal Diet in the Presence or Absence of Microbes Associated With Gut Immune Activation, Regulatory Imbalance, and Altered Cathelicidin Antimicrobial Peptide

    Science.gov (United States)

    Patrick, Christopher; Wang, Gen-Sheng; Lefebvre, David E.; Crookshank, Jennifer A.; Sonier, Brigitte; Eberhard, Chandra; Mojibian, Majid; Kennedy, Christopher R.; Brooks, Stephen P.J.; Kalmokoff, Martin L.; Maglio, Mariantonia; Troncone, Riccardo; Poussier, Philippe; Scott, Fraser W.

    2013-01-01

    We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely play a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetes-promoting cereal diets or a protective low-antigen hydrolyzed casein (HC) diet, and T1D incidence was monitored. Fecal microbiota 16S rRNA genes, immune cell distribution, and gene expression in the jejunum were analyzed. T1D was highest in cereal-SPF (65%) and cereal-GF rats (53%) but inhibited and delayed in HC-fed counterparts. Nearly all HC-GF rats remained diabetes-free, whereas HC-fed SPF rats were less protected (7 vs. 29%). Bacterial communities differed in SPF rats fed cereal compared with HC. Cereal-SPF rats displayed increased gut CD3+ and CD8α+ lymphocytes, ratio of Ifng to Il4 mRNA, and Lck expression, indicating T-cell activation. The ratio of CD3+ T cells expressing the Treg marker Foxp3+ was highest in HC-GF and lowest in cereal-SPF rats. Resident CD163+ M2 macrophages were increased in HC-protected rats. The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet–protected rats, and CAMP+ cells colocalized with CD163. A cereal diet was a stronger promoter of T1D than gut microbes in association with impaired gut immune homeostasis. PMID:23349499

  12. Interorganizational Cooperation

    Science.gov (United States)

    2016-10-12

    prices in the local economy, undermining progress. Communication between the US military and NGOs can promote US national interests and policy. Civil...Lo gis tic s M an ag em en t a nd Re so ur ce S up po rt #1 0 - O il a nd H az ar do us M at er ial s Re sp on se Domestic Coordination...terrorist activities, with a particular focus in Afghanistan and Pakistan . The FBI created the CBRNE [Chemical, Biological, Radiological, Nuclear

  13. A universal algorithm for genome-wide in silicio identification of biologically significant gene promoter putative cis-regulatory-elements; identification of new elements for reactive oxygen species and sucrose signaling in Arabidopsis.

    Science.gov (United States)

    Geisler, Matt; Kleczkowski, Leszek A; Karpinski, Stanislaw

    2006-02-01

    Short motifs of many cis-regulatory elements (CREs) can be found in the promoters of most Arabidopsis genes, and this raises the question of how their presence can confer specific regulation. We developed a universal algorithm to test the biological significance of CREs by first identifying every Arabidopsis gene with a CRE and then statistically correlating the presence or absence of the element with the gene expression profile on multiple DNA microarrays. This algorithm was successfully verified for previously characterized abscisic acid, ethylene, sucrose and drought responsive CREs in Arabidopsis, showing that the presence of these elements indeed correlates with treatment-specific gene induction. Later, we used standard motif sampling methods to identify 128 putative motifs induced by excess light, reactive oxygen species and sucrose. Our algorithm was able to filter 20 out of 128 novel CREs which significantly correlated with gene induction by either heat, reactive oxygen species and/or sucrose. The position, orientation and sequence specificity of CREs was tested in silicio by analyzing the expression of genes with naturally occurring sequence variations. In three novel CREs the forward orientation correlated with sucrose induction and the reverse orientation with sucrose suppression. The functionality of the predicted novel CREs was experimentally confirmed using Arabidopsis cell-suspension cultures transformed with short promoter fragments or artificial promoters fused with the GUS reporter gene. Our genome-wide analysis opens up new possibilities for in silicio verification of the biological significance of newly discovered CREs, and allows for subsequent selection of such CREs for experimental studies.

  14. Reward, Punishment, and Cooperation : A Meta-Analysis

    NARCIS (Netherlands)

    Balliet, Daniel; Mulder, Laetitia B.; Van Lange, Paul A. M.

    How effective are rewards (for cooperation) and punishment (for noncooperation) as tools to promote cooperation in social dilemmas or situations when immediate self-interest and longer term collective interest conflict? What variables can promote the impact of these incentives? Although such

  15. Reward, Punishment, and Cooperation: A Meta-Analysis

    Science.gov (United States)

    Balliet, Daniel; Mulder, Laetitia B.; Van Lange, Paul A. M.

    2011-01-01

    How effective are rewards (for cooperation) and punishment (for noncooperation) as tools to promote cooperation in social dilemmas or situations when immediate self-interest and longer term collective interest conflict? What variables can promote the impact of these incentives? Although such questions have been examined, social and behavioral…

  16. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  17. Promoting academia-industry cooperation for innovation

    NARCIS (Netherlands)

    Crul, M.R.M.; Schnitzer, H.

    2010-01-01

    Innovation and Innovation Management are essential instruments and methodologies to manage the changes that society and its productive sector are facing in order to find the right balance between competitiveness, trade demands, social equity and sustainable development. A clear role in this can be

  18. The virtual cooperation platform in enterprise and supplier cooperation models.

    Science.gov (United States)

    Chang, Che-Wei; Wu, Cheng-Ru; Liao, Chia-Chun

    2010-08-01

    Abstract This study examines the use of the virtual enterprise network supplier supply-chain model of business behavior in creating synergies of cooperation. To explore virtual network behavior, it evaluates 60 samples, taken from of a few supply chains, and 17 items meeting certain behavioral criteria. Such an analysis may help to reduce costs and processing time effectively, as well as promote effective communication. Furthermore, the study of behavior in this electronic setting is a reliable and useful assessment method.

  19. PREFACE: Cooperative dynamics Cooperative dynamics

    Science.gov (United States)

    Gov, Nir

    2011-09-01

    The dynamics within living cells are dominated by non-equilibrium processes that consume chemical energy (usually in the form of ATP, adenosine triphosphate) and convert it into mechanical forces and motion. The mechanisms that allow this conversion process are mostly driven by the components of the cytoskeleton: (i) directed (polar) polymerization of filaments (either actin or microtubules) and (ii) molecular motors. The forces and motions produced by these two components of the cytoskeleton give rise to the formation of cellular shapes, and drive the intracellular transport and organization. It is clear that these systems present a multi-scale challenge, from the physics of the molecular processes to the organization of many interacting units. Understanding the physical nature of these systems will have a large impact on many fundamental problems in biology and break new grounds in the field of non-equilibrium physics. This field of research has seen a rapid development over the last ten years. Activities in this area range from theoretical and experimental work on the underlying fundamental (bio)physics at the single-molecule level, to investigations (in vivo and in vitro) of the dynamics and patterns of macroscopic pieces of 'living matter'. In this special issue we have gathered contributions that span the whole spectrum of length- and complexity-scales in this field. Some of the works demonstrate how active forces self-organize within the polymerizing cytoskeleton, on the level of cooperative cargo transport via motors or due to active fluxes at the cell membrane. On a larger scale, it is shown that polar filaments coupled to molecular motors give rise to a huge variety of surprising dynamics and patterns: spontaneously looping rings of gliding microtubules, and emergent phases of self-organized filaments and motors in different geometries. All of these articles share the common feature of being out-of-equilibrium, driven by metabolism. As demonstrated here

  20. Drought-responsive genes expressed predominantly in root tissues are enriched with homotypic cis-regulatory clusters in promoters of major cereal crops

    Directory of Open Access Journals (Sweden)

    Muhammad Ramzan Khan

    2017-06-01

    Full Text Available The root appears to be the most relevant organ for breeding drought stress tolerance. However, our knowledge about temporal and spatial regulation of drought-associated genes in the root remains fragmented, especially in crop plants. We performed a meta-analysis of expression divergence of essential drought-inducible genes and analyzed their association with cis-elements in model crops and major cereal crops. Our analysis of 42 selected drought-inducible genes revealed that these are expressed primarily in roots, followed by shoot, leaf, and inflorescence tissues, especially in wheat. Quantitative real-time RT-PCR analysis confirmed higher expression of TaDREB2 and TaAQP7 in roots, correlated with extensive rooting and drought-stress tolerance in wheat. A promoter scan up to 2 kb upstream of the translation start site using phylogenetic footprinting revealed 708 transcription factor binding sites, including drought response elements (DREs, auxin response elements (AuxREs, MYCREs/MYBREs, ABAREs, and ERD1 in 19 selected genes. Interestingly, these elements were organized into clusters of overlapping transcription factor binding sites known as homotypic clusters (HCTs, which modulate drought physiology in plants. Taken together, these results revealed the expression preeminence of major drought-inducible genes in the root, suggesting its crucial role in drought adaptation. The occurrence of HCTs in drought-inducible genes highlights the putative evolutionary modifications of crop plants in developing drought adaptation. We propose that these DNA motifs can be used as molecular markers for breeding drought-resilient cultivars, particularly in the cereal crops.

  1. 75 FR 64728 - Cooperative Operating Philosophy-Serving the Members of Farm Credit System Institutions

    Science.gov (United States)

    2010-10-20

    ... Cooperative Operating Philosophy--Serving the Members of Farm Credit System Institutions AGENCY: Farm Credit... Board Hereby Adopts the Following Policy Statement: Cooperative Operating Philosophy--Serving the Member..., ``Implementation of cooperative principles.'' \\2\\ See FCA Policy Statement ``Regulatory Philosophy'' (FCA-PS- 59...

  2. Informe sobre a cooperação Brasil-Canadá em promoção da saúde Report on the cooperation Brazil-Canada in health promotion

    Directory of Open Access Journals (Sweden)

    Lenira Zancan

    2004-09-01

    Full Text Available O trabalho relata a experiência de cooperação no campo da Promoção da Saúde, estabelecida entre a Escola Nacional de Saúde Pública (ENSP, a Associação Brasileira de Saúde Coletiva (Abrasco e a Associação Canadense de Saúde Pública (CPHA nos últimos quatro anos. Tal experiência tem evidenciado que a promoção da saúde e o desenvolvimento local são guiados por valores comuns e estratégias de ação similares, fundamentados em participação social, empowerment e colaboração intersetorial. No Brasil, as estratégias para promoção da saúde e desenvolvimento local ainda são insipientes e, por sua complexidade, necessitam ser sistematicamente analisadas. Nesse contexto, os parceiros canadenses e brasileiros se propõem, através de um novo Projeto de Cooperação, apoiar municípios selecionados nas várias regiões do país, na implementação e avaliação de intervenções em promoção da saúde e na construção de capacidades para o desenvolvimento local e ação intersetorial para a saúde. Essa agenda colaborativa toma por base as teorias da avaliação participativa, contribuindo para a construção de modelos e ferramentas de reflexive practices em desenvolvimento local e promoção da saúde, criando processos sustentáveis de melhoria dos ambientes físicos e sociais com impacto na saúde.This report presents the Project Development Phase of a Cooperation on Health Promotion involving the National School of Public Health (ENSP, the Brazilian Association of Collective Health (ABRASCO, and the Canadian Association of Public Health (CPHA. That experience evidenced that health promotion and local development are guided by common values and similar strategies for action, which are based on public participation, empowerment, and intersectoral collaboration. In Brazil the strategies for health promotion and local development are still undergoing and, for theirs complexity, need to be systematically analyzed. Within this

  3. Inter-Municipal Cooperation in the Development of Industrial Parks and Tax Redistribution: The Road to Hell is Paved with Good Intentions

    Directory of Open Access Journals (Sweden)

    Razin Eran

    2016-06-01

    Full Text Available Inter-municipal cooperation mechanisms have been promoted as flexible tools, reflecting the transition from government to governance in a new network economy and eliminating the need to engage in redrawing clear-cut boundaries in the context of soft spaces with fuzzy boundaries. An evaluation of inter-municipal cooperation in the development of industrial parks and tax revenue redistribution in Israel, from the first 1992 initiative to imposed redistribution in 2014/15, reveals how an initiative ’from below’ has been adopted and encouraged ’from above’, finally used by the central state as a tool of control, to serve its own objectives. It highlights the inherent temptation for top-down imposition, embedded in bottom-up cooperation mechanisms, calling for light-touch regulatory legislation and opting for gently imposed solutions where needed.

  4. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune......-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles...

  5. Gr-1⁺CD11b⁺ immature myeloid cells (IMC) promote resistance of pro-inflammatory T cells to suppression by regulatory T cells in atherosclerotic Apo E- deficient mice.

    Science.gov (United States)

    Chen, Yulin; Jian, Ying; Liu, Minjie; Zhong, Liang; Zhang, Fang; Yang, Weifeng; Xu, Zhao; Chen, Guofan; Liu, Yuhua

    2014-01-01

    Accumulating evidence indicates that both defects in Treg numbers and/or function as well as resistance of effector T cells to suppression may contribute to the development of human chronic inflammatory diseases. However, which mechanism involved in the progression of atherosclerosis remains unclear. In this study, we evaluated the production and function of CD4⁺ inflammatory and regulatory T cells in atherosclerosis-prone mice. We found that the hyperactivity and unresponsiveness to Treg-mediated suppression of inflammatory CD4⁺ T cells occurred in the progression of atherosclerosis, though Treg cells were present in very large numbers and fully functional. We further found that Gr-1⁺CD11b⁺ immature myeloid cells were significantly accumulated in atherosclerotic Apo E⁻/⁻ mice, and they promoted resistance of inflammatory CD4⁺ T cells to Treg-mediated suppression in vitro and in vivo. we further confirmed that Gr-1⁺CD11b⁺ immature myeloid cells produced high level of interleukin 6 which was at least partially responsible for inducing unresponsiveness of inflammatory CD4⁺ T cells to suppression via activation of Jak/Stat signaling pathway. Taken together, these findings might provide new insights to explore potential targets for immune therapeutic intervention in atherosclerosis.

  6. Collective action : a regulatory focus perspective

    NARCIS (Netherlands)

    Zaal, Maarten Pieter

    2012-01-01

    In this dissertation I investigate how individuals respond to collective disadvantage from the perspective of regulatory focus theory. Regulatory focus theory distinguishes between two motivational systems: promotion focus, the system in charge of the approach of positive end-states, and prevention

  7. Cooperative Learning Principles Enhance Online Interaction

    Directory of Open Access Journals (Sweden)

    George Jacobs

    2015-04-01

    Full Text Available Research suggests that cooperative interactions are associated with enhanced cognitive and affective outcomes. This paper describes eight principles that can be used to promote such interactions among students working in online environments. The principles derive from a well-established approach to education, known variously as cooperative learning and collaborative learning. Each principle is explained as to what it means, why it is important and how it can be deployed. The eight principles are heterogeneous grouping, teaching collaborative skills, group autonomy, maximum peer interactions, equal opportunity to participate, individual accountability, positive interdependence and cooperation as a value.

  8. Fashion, cooperation, and social interactions.

    Science.gov (United States)

    Cao, Zhigang; Gao, Haoyu; Qu, Xinglong; Yang, Mingmin; Yang, Xiaoguang

    2013-01-01

    Fashion plays such a crucial rule in the evolution of culture and society that it is regarded as a second nature to the human being. Also, its impact on economy is quite nontrivial. On what is fashionable, interestingly, there are two viewpoints that are both extremely widespread but almost opposite: conformists think that what is popular is fashionable, while rebels believe that being different is the essence. Fashion color is fashionable in the first sense, and Lady Gaga in the second. We investigate a model where the population consists of the afore-mentioned two groups of people that are located on social networks (a spatial cellular automata network and small-world networks). This model captures two fundamental kinds of social interactions (coordination and anti-coordination) simultaneously, and also has its own interest to game theory: it is a hybrid model of pure competition and pure cooperation. This is true because when a conformist meets a rebel, they play the zero sum matching pennies game, which is pure competition. When two conformists (rebels) meet, they play the (anti-) coordination game, which is pure cooperation. Simulation shows that simple social interactions greatly promote cooperation: in most cases people can reach an extraordinarily high level of cooperation, through a selfish, myopic, naive, and local interacting dynamic (the best response dynamic). We find that degree of synchronization also plays a critical role, but mostly on the negative side. Four indices, namely cooperation degree, average satisfaction degree, equilibrium ratio and complete ratio, are defined and applied to measure people's cooperation levels from various angles. Phase transition, as well as emergence of many interesting geographic patterns in the cellular automata network, is also observed.

  9. Fashion, cooperation, and social interactions.

    Directory of Open Access Journals (Sweden)

    Zhigang Cao

    Full Text Available Fashion plays such a crucial rule in the evolution of culture and society that it is regarded as a second nature to the human being. Also, its impact on economy is quite nontrivial. On what is fashionable, interestingly, there are two viewpoints that are both extremely widespread but almost opposite: conformists think that what is popular is fashionable, while rebels believe that being different is the essence. Fashion color is fashionable in the first sense, and Lady Gaga in the second. We investigate a model where the population consists of the afore-mentioned two groups of people that are located on social networks (a spatial cellular automata network and small-world networks. This model captures two fundamental kinds of social interactions (coordination and anti-coordination simultaneously, and also has its own interest to game theory: it is a hybrid model of pure competition and pure cooperation. This is true because when a conformist meets a rebel, they play the zero sum matching pennies game, which is pure competition. When two conformists (rebels meet, they play the (anti- coordination game, which is pure cooperation. Simulation shows that simple social interactions greatly promote cooperation: in most cases people can reach an extraordinarily high level of cooperation, through a selfish, myopic, naive, and local interacting dynamic (the best response dynamic. We find that degree of synchronization also plays a critical role, but mostly on the negative side. Four indices, namely cooperation degree, average satisfaction degree, equilibrium ratio and complete ratio, are defined and applied to measure people's cooperation levels from various angles. Phase transition, as well as emergence of many interesting geographic patterns in the cellular automata network, is also observed.

  10. Dismantlement of nuclear facilities decommissioned from the Russian navy: Enhancing regulatory supervision of nuclear and radiation safety

    Energy Technology Data Exchange (ETDEWEB)

    Sneve, M.K.

    2013-03-01

    The availability of up to date regulatory norms and standards for nuclear and radiation safety, relevant to the management of nuclear legacy situations, combined with effective and efficient regulatory procedures for licensing and monitoring compliance, are considered to be extremely important. Accordingly the NRPA has set up regulatory cooperation programs with corresponding authorities in the Russian Federation. Cooperation began with the civilian regulatory authorities and was more recently extended to include the military authority and this joint cooperation supposed to develop the regulatory documents to improve supervision over nuclear and radiation safety while managing the nuclear military legacy facilities in Northwest Russia and other regions of the country. (Author)

  11. Regulatory aspects on nanomedicines.

    Science.gov (United States)

    Sainz, Vanessa; Conniot, João; Matos, Ana I; Peres, Carina; Zupancic, Eva; Moura, Liane; Silva, Liana C; Florindo, Helena F; Gaspar, Rogério S

    2015-12-18

    Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches. However, the wide range of application of nanomedicines demands a profound knowledge and characterization of these complex products. Their properties need to be extensively understood to avoid unpredicted effects on patients, such as potential immune reactivity. Research policy and alliances have been bringing together scientists, regulators, industry, and, more frequently in recent years, patient representatives and patient advocacy institutions. In order to successfully enhance the development of new technologies, improved strategies for research-based corporate organizations, more integrated research tools dealing with appropriate translational requirements aiming at clinical development, and proactive regulatory policies are essential in the near future. This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market. Regulatory Science aspects driving a faster and safer development of nanomedicines will be a central issue for the next years. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Evolution of cooperation on stochastic dynamical networks.

    Science.gov (United States)

    Wu, Bin; Zhou, Da; Fu, Feng; Luo, Qingjun; Wang, Long; Traulsen, Arne

    2010-06-30

    Cooperative behavior that increases the fitness of others at a cost to oneself can be promoted by natural selection only in the presence of an additional mechanism. One such mechanism is based on population structure, which can lead to clustering of cooperating agents. Recently, the focus has turned to complex dynamical population structures such as social networks, where the nodes represent individuals and links represent social relationships. We investigate how the dynamics of a social network can change the level of cooperation in the network. Individuals either update their strategies by imitating their partners or adjust their social ties. For the dynamics of the network structure, a random link is selected and breaks with a probability determined by the adjacent individuals. Once it is broken, a new one is established. This linking dynamics can be conveniently characterized by a Markov chain in the configuration space of an ever-changing network of interacting agents. Our model can be analytically solved provided the dynamics of links proceeds much faster than the dynamics of strategies. This leads to a simple rule for the evolution of cooperation: The more fragile links between cooperating players and non-cooperating players are (or the more robust links between cooperators are), the more likely cooperation prevails. Our approach may pave the way for analytically investigating coevolution of strategy and structure.

  13. Evolution of cooperation on stochastic dynamical networks.

    Directory of Open Access Journals (Sweden)

    Bin Wu

    Full Text Available Cooperative behavior that increases the fitness of others at a cost to oneself can be promoted by natural selection only in the presence of an additional mechanism. One such mechanism is based on population structure, which can lead to clustering of cooperating agents. Recently, the focus has turned to complex dynamical population structures such as social networks, where the nodes represent individuals and links represent social relationships. We investigate how the dynamics of a social network can change the level of cooperation in the network. Individuals either update their strategies by imitating their partners or adjust their social ties. For the dynamics of the network structure, a random link is selected and breaks with a probability determined by the adjacent individuals. Once it is broken, a new one is established. This linking dynamics can be conveniently characterized by a Markov chain in the configuration space of an ever-changing network of interacting agents. Our model can be analytically solved provided the dynamics of links proceeds much faster than the dynamics of strategies. This leads to a simple rule for the evolution of cooperation: The more fragile links between cooperating players and non-cooperating players are (or the more robust links between cooperators are, the more likely cooperation prevails. Our approach may pave the way for analytically investigating coevolution of strategy and structure.

  14. Statistical physics of human cooperation

    Science.gov (United States)

    Perc, Matjaž; Jordan, Jillian J.; Rand, David G.; Wang, Zhen; Boccaletti, Stefano; Szolnoki, Attila

    2017-05-01

    Extensive cooperation among unrelated individuals is unique to humans, who often sacrifice personal benefits for the common good and work together to achieve what they are unable to execute alone. The evolutionary success of our species is indeed due, to a large degree, to our unparalleled other-regarding abilities. Yet, a comprehensive understanding of human cooperation remains a formidable challenge. Recent research in the social sciences indicates that it is important to focus on the collective behavior that emerges as the result of the interactions among individuals, groups, and even societies. Non-equilibrium statistical physics, in particular Monte Carlo methods and the theory of collective behavior of interacting particles near phase transition points, has proven to be very valuable for understanding counterintuitive evolutionary outcomes. By treating models of human cooperation as classical spin models, a physicist can draw on familiar settings from statistical physics. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among humans often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. The complexity of solutions therefore often surpasses that observed in physical systems. Here we review experimental and theoretical research that advances our understanding of human cooperation, focusing on spatial pattern formation, on the spatiotemporal dynamics of observed solutions, and on self-organization that may either promote or hinder socially favorable states.

  15. Cooperative Tagging Center (CTC)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Cooperative Tagging Center (CTC) began as the Cooperative Game Fish Tagging Program (GTP) at Woods Hole Oceanographic Institute (WHOI) in 1954. The GTP was...

  16. Regulatory focus and human values

    Directory of Open Access Journals (Sweden)

    Keller Johannes

    2017-01-01

    Full Text Available The present article connects two approaches to the study of human motivation and behavior: The Schwartz model of human values and Higgins’ regulatory focus theory. Considering a prominent model of human motivation - the Rubicon Model of Action Phases - reveals that although both approaches refer to goals and standards as crucial constructs, human values are specifically relevant concerning the so-called deliberation and evaluation phases whereas selfregulatory orientations are specifically relevant concerning the volitional phases (i.e., planning and action. It may be due to the selective focus on specific aspects of human motivation that up to date hardly any (empirical work has tried to connect human values and selfregulatory orientations. The reported studies assessed the relation between the endorsement of values proposed in the Schwartz model of human values and individual differences in the two self-regulatory orientations (promotion and prevention proposed in regulatory focus theory. Findings reveal that prevention-focused self-regulation is positively related to conservation values (security, conformity and negatively related to values reflecting openness to change (stimulation, self-direction. Moreover, promotion-focused self-regulation was positively related to self-enhancement values (power, achievement and negatively related to values reflecting self-transcendence (universalism, benevolence. In addition, the observed relations were found using different instruments to measure human values and self-regulatory orientations. In combination, the observed findings support the proposed two-dimensional structure of the value system as well as fundamental assumptions of regulatory focus theory.

  17. Positive- and negative-acting regulatory elements contribute to the tissue-specific expression of INNER NO OUTER, a YABBY-type transcription factor gene in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Simon Marissa K

    2012-11-01

    Full Text Available Abstract Background The INNER NO OUTER (INO gene, which encodes a YABBY-type transcription factor, specifies and promotes the growth of the outer integument of the ovule in Arabidopsis. INO expression is limited to the abaxial cell layer of the developing outer integument of the ovule and is regulated by multiple regions of the INO promoter, including POS9, a positive element that when present in quadruplicate can produce low-level expression in the normal INO pattern. Results Significant redundancy in activity between different regions of the INO promoter is demonstrated. For specific regulatory elements, multimerization or the addition of the cauliflower mosaic virus 35S general enhancer was able to activate expression of reporter gene constructs that were otherwise incapable of expression on their own. A new promoter element, POS6, is defined and is shown to include sufficient positive regulatory information to reproduce the endogenous pattern of expression in ovules, but other promoter regions are necessary to fully suppress expression outside of ovules. The full-length INO promoter, but not any of the INO promoter deletions tested, is able to act as an enhancer-blocking insulator to prevent the ectopic activation of expression by the 35S enhancer. Sequence conservation between the promoter regions of Arabidopsis thaliana, Brassica oleracea and Brassica rapa aligns closely with the functional definition of the POS6 and POS9 regions, and with a defined INO minimal promoter. The B. oleracea INO promoter is sufficient to promote a similar pattern and level of reporter gene expression in Arabidopsis to that observed for the Arabidopsis promoter. Conclusions At least two independent regions of the INO promoter contain sufficient regulatory information to direct the specific pattern but not the level of INO gene expression. These regulatory regions act in a partially redundant manner to promote the expression in a specific pattern in the ovule and

  18. Reward and cooperation in the spatial public goods game

    Science.gov (United States)

    Szolnoki, A.; Perc, M.

    2010-11-01

    The promise of punishment and reward in promoting public cooperation is debatable. While punishment is traditionally considered more successful than reward, the fact that the cost of punishment frequently fails to offset gains from enhanced cooperation has lead some to reconsider reward as the main catalyst behind collaborative efforts. Here we elaborate on the "stick vs. carrot" dilemma by studying the evolution of cooperation in the spatial public goods game, where besides the traditional cooperators and defectors, rewarding cooperators supplement the array of possible strategies. The latter are willing to reward cooperative actions at a personal cost, thus effectively downgrading pure cooperators to second-order free-riders due to their unwillingness to bear these additional costs. Consequently, we find that defection remains viable, especially if the rewarding is costly. Rewards, however, can promote cooperation, especially if the synergetic effects of cooperation are low. Surprisingly, moderate rewards may promote cooperation better than high rewards, which is due to the spontaneous emergence of cyclic dominance between the three strategies.

  19. What is a cooperative?

    Science.gov (United States)

    Kimberly Zeuli

    2006-01-01

    Groups of individuals throughout time have worked together in pursuit of common goals. The earliest forms of hunting and agriculture required a great deal of cooperation among humans. Although the word "cooperative" can be applied to many different types of group activities, in this publication it refers to a formal business model. Cooperative businesses are...

  20. 76 FR 36532 - Gregory R. Swecker, Beverly F. Swecker v. Midland Power Cooperative, State of Iowa; Notice of...

    Science.gov (United States)

    2011-06-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Gregory R. Swecker, Beverly F. Swecker v. Midland Power Cooperative, State... Utility Regulatory Policies Act (PURPA) against Midland Power Cooperative and the State of Iowa...

  1. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  2. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  3. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  4. Designing for cooperation - cooperating in design

    DEFF Research Database (Denmark)

    Kyng, Morten

    1991-01-01

    This article will discuss how to design computer applications that enhance the quality of work and products, and will relate the discussion to current themes in the field of Computer-Supported Cooperative Work (CSCW). Cooperation is a key element of computer use and work practice, yet here...... a specific "CSCW approach is not taken." Instead the focus is cooperation as an important aspect of work that should be integrated into most computer support efforts in order to develop successful computer support, however, other aspects such as power, conflict and control must also be considered....

  5. Cooperative strategies European perspectives

    CERN Document Server

    Killing, J Peter

    1997-01-01

    Cooperative Strategies: European Perspectives is one of three geographically targeted volumes in which the contributors present the most current research on topics such as advances in theories of cooperative strategies, the formation of cooperative alliances, the dynamics of partner relationships, and the role of information and knowledge in cooperative alliances. Blending conceptual insights with empirical analyses, the contributors highlight commonalities and differences across national, cultural, and trade zones. The chapters in this volume are anchored in a wide set of theoretical approaches, conceptual frameworks, and models, illustrating how rich the area of cooperative strategies is for scholarly inquiry.

  6. Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1

    Science.gov (United States)

    Sankar, Savita; Yellajoshyula, Dhananjay; Zhang, Bo; Teets, Bryan; Rockweiler, Nicole; Kroll, Kristen L.

    2016-01-01

    Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment. PMID:27881878

  7. The principle of open and voluntary membership. Legal and enforcing economic consequences practice, in the Costa Rican cooperative movement

    Directory of Open Access Journals (Sweden)

    Ligia Roxana Sánchez Boza

    2017-12-01

    Full Text Available The basis of the cooperative principle of free adhesion or voluntary adherence is found in the constitutional rules, which define the Right of Association. The legal and regulatory development of these rules is done through cooperative laws, acts of constitution and other rules of affiliation and disaffiliation of cooperatives. The application of the principle in the study must be interdependent with the rest of the Cooperative Principles as well as the Values of the Cooperatives, in order to ensure adequate protection for both the associate and the associated cooperative. In this paper of the principle in the study is made through the election of a cooperative, in most cases, credit unions. These cooperatives, for reasons of their economic activity, have more legal and regulatory regulations compared to the other types of cooperatives, according the effects of affiliation and disaffiliation.Received: 01 June 2017Accepted: 14 October 2017Published online: 22 December 2017

  8. To cooperate or not to cooperate

    DEFF Research Database (Denmark)

    Wessels, Josepha Ivanka

    To Cooperate or not to Cooperate...? discusses results of a research project to study the rehabilitation of 1500-year old water tunnels, so called "qanats", in Syria. Communities all over the world are using traditional technologies to extract drinkingwater, irrigate their lands and feed...... their livestock. But these often sustainable and ancient ways to make use of groundwater are in rapid decline worldwide. A research project started in 1999 to study the rehabilitation of 1500-year old water tunnels called "qanats"in Syria. To Cooperate or not to Cooperate...? discusses results and outcomes...... divers theoretical and conceptual frameworks to study collective action with a human ecosystem approach and develop one with a stronger anthropological reference....

  9. Social Stratification and Cooperative Behavior in Spatial Prisoners' Dilemma Games.

    Science.gov (United States)

    Lu, Peng; Zheng, Xiaoping

    2015-01-01

    It has been a long-lasting pursuit to promote cooperation, and this study aims to promote cooperation via the combination of social stratification and the spatial prisoners' dilemma game. It is previously assumed that agents share the identical payoff matrix, but the stratification or diversity exists and exerts influences in real societies. Thus, two additional classes, elites and scoundrels, derive from and coexist with the existing class, commons. Three classes have different payoff matrices. We construct a model where agents play the prisoners' dilemma game with neighbors. It indicates that stratification and temptation jointly influence cooperation. Temptation permanently reduces cooperation; elites play a positive role in promoting cooperation while scoundrels undermine it. As the temptation getting larger and larger, elites play a more and more positive and critical role while scoundrels' negative effect becomes weaker and weaker, and it is more obvious when temptation goes beyond its threshold.

  10. Social Stratification and Cooperative Behavior in Spatial Prisoners' Dilemma Games.

    Directory of Open Access Journals (Sweden)

    Peng Lu

    Full Text Available It has been a long-lasting pursuit to promote cooperation, and this study aims to promote cooperation via the combination of social stratification and the spatial prisoners' dilemma game. It is previously assumed that agents share the identical payoff matrix, but the stratification or diversity exists and exerts influences in real societies. Thus, two additional classes, elites and scoundrels, derive from and coexist with the existing class, commons. Three classes have different payoff matrices. We construct a model where agents play the prisoners' dilemma game with neighbors. It indicates that stratification and temptation jointly influence cooperation. Temptation permanently reduces cooperation; elites play a positive role in promoting cooperation while scoundrels undermine it. As the temptation getting larger and larger, elites play a more and more positive and critical role while scoundrels' negative effect becomes weaker and weaker, and it is more obvious when temptation goes beyond its threshold.

  11. The Director-General awards Professor Herwig Schopper, President of the SESAME Council, UNESCO's gold Albert Einstein medal in recognition of his outstanding contribution to the promotion of international cooperation, the advancement of the physical sciences and UNESCO's science programme.

    CERN Multimedia

    2004-01-01

    SESAME is an epitome of what international cooperation should be and there is no doubt that Professor Schopper's leadership has been one of the important factors that has allowed the project to reach its current advanced stageHerwig Schopper is an outstanding scientist who has made a remarkable contribution to the advancement of science in areas such as nuclear and particle physics.

  12. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  13. Determinants of public cooperation in multiplex networks

    Science.gov (United States)

    Battiston, Federico; Perc, Matjaž; Latora, Vito

    2017-07-01

    Synergies between evolutionary game theory and statistical physics have significantly improved our understanding of public cooperation in structured populations. Multiplex networks, in particular, provide the theoretical framework within network science that allows us to mathematically describe the rich structure of interactions characterizing human societies. While research has shown that multiplex networks may enhance the resilience of cooperation, the interplay between the overlap in the structure of the layers and the control parameters of the corresponding games has not yet been investigated. With this aim, we consider here the public goods game on a multiplex network, and we unveil the role of the number of layers and the overlap of links, as well as the impact of different synergy factors in different layers, on the onset of cooperation. We show that enhanced public cooperation emerges only when a significant edge overlap is combined with at least one layer being able to sustain some cooperation by means of a sufficiently high synergy factor. In the absence of either of these conditions, the evolution of cooperation in multiplex networks is determined by the bounds of traditional network reciprocity with no enhanced resilience. These results caution against overly optimistic predictions that the presence of multiple social domains may in itself promote cooperation, and they help us better understand the complexity behind prosocial behavior in layered social systems.

  14. The evolution of cooperation on geographical networks

    Science.gov (United States)

    Li, Yixiao; Wang, Yi; Sheng, Jichuan

    2017-11-01

    We study evolutionary public goods game on geographical networks, i.e., complex networks which are located on a geographical plane. The geographical feature effects in two ways: In one way, the geographically-induced network structure influences the overall evolutionary dynamics, and, in the other way, the geographical length of an edge influences the cost when the two players at the two ends interact. For the latter effect, we design a new cost function of cooperators, which simply assumes that the longer the distance between two players, the higher cost the cooperator(s) of them have to pay. In this study, network substrates are generated by a previous spatial network model with a cost-benefit parameter controlling the network topology. Our simulations show that the greatest promotion of cooperation is achieved in the intermediate regime of the parameter, in which empirical estimates of various railway networks fall. Further, we investigate how the distribution of edges' geographical costs influences the evolutionary dynamics and consider three patterns of the distribution: an approximately-equal distribution, a diverse distribution, and a polarized distribution. For normal geographical networks which are generated using intermediate values of the cost-benefit parameter, a diverse distribution hinders the evolution of cooperation, whereas a polarized distribution lowers the threshold value of the amplification factor for cooperation in public goods game. These results are helpful for understanding the evolution of cooperation on real-world geographical networks.

  15. Mobility, fitness collection, and the breakdown of cooperation.

    Science.gov (United States)

    Gelimson, Anatolij; Cremer, Jonas; Frey, Erwin

    2013-04-01

    The spatial arrangement of individuals is thought to overcome the dilemma of cooperation: When cooperators engage in clusters, they might share the benefit of cooperation while being more protected against noncooperating individuals, who benefit from cooperation but save the cost of cooperation. This is paradigmatically shown by the spatial prisoner's dilemma model. Here, we study this model in one and two spatial dimensions, but explicitly take into account that in biological setups, fitness collection and selection are separated processes occurring mostly on vastly different time scales. This separation is particularly important to understand the impact of mobility on the evolution of cooperation. We find that even small diffusive mobility strongly restricts cooperation since it enables noncooperative individuals to invade cooperative clusters. Thus, in most biological scenarios, where the mobility of competing individuals is an irrefutable fact, the spatial prisoner's dilemma alone cannot explain stable cooperation, but additional mechanisms are necessary for spatial structure to promote the evolution of cooperation. The breakdown of cooperation is analyzed in detail. We confirm the existence of a phase transition, here controlled by mobility and costs, which distinguishes between purely cooperative and noncooperative absorbing states. While in one dimension the model is in the class of the voter model, it belongs to the directed percolation universality class in two dimensions.

  16. Models of conflict and cooperation

    CERN Document Server

    Gillman, Rick

    2009-01-01

    Models of Conflict and Cooperation is a comprehensive, introductory, game theory text for general undergraduate students. As a textbook, it provides a new and distinctive experience for students working to become quantitatively literate. Each chapter begins with a "dialogue" that models quantitative discourse while previewing the topics presented in the rest of the chapter. Subsequent sections develop the key ideas starting with basic models and ending with deep concepts and results. Throughout all of the sections, attention is given to promoting student engagement with the material through re

  17. Biham—Middleton—Levine model in consideration of cooperative willingness

    Science.gov (United States)

    Pan, Wei; Xue, Yu; Zhao, Rui; Lu, Wei-Zhen

    2014-05-01

    In this paper, the Biham—Middleton—Levine (BML) model with consideration of cooperative willingness has been proposed to study the traffic flow in urban networks. An evolutionary game with a cooperative willingness profile is introduced to deal with conflicts between disturbing neighbors. Simulation results suggest that imitating cooperative willingness can ease the effect of premature seizure on traffic flow due to the introduction of evolutionary games. Phase diagrams with a strategy profile and cooperative willingness profile have been investigated in detail. Our findings also prove that by imitating the more successful, cooperative willingness instead of simply the more successful strategies, the evolution of cooperation is significantly promoted, hence improving the order of cooperation and relieving the pressure of traffic networks.

  18. The Global Diffusion of Regulatory Instruments: The Making of a New International Environmental Regime

    Directory of Open Access Journals (Sweden)

    Kerstin Tews

    2004-12-01

    Full Text Available During the 1990s a new regulatory pattern in domestic environmental policymaking has been emerging which is characterized by an increasing use of cooperative, informational and marked-based instruments. This pattern is to an important extent a result of international policy diffusion the cross-national spread of policy innovations driven by information flows rather than hierarchical or collective decision-making within international institutions. Based on four case studies, the paper demonstrates empirically how horizontal diffusion processes accompanied by information and recommendations from international organizations have led to the adoption of new regulatory instruments in an increasing number of countries and how these individual national adoptions add up to an emerging regulatory structure at the international level. At the macro-level, the case studies explore how diffusion interacts with the other two major international mechanisms of domestic policy change: legal harmonization and coercive imposition. Especially within the European Union a typical pattern of horizontal diffusion between individual member states, followed by vertical diffusion from the national to the EU-level and finally leading to an EU-wide legal harmonization through EC-directives can be identified. At the micro-level, the paper investigates which factors promote or obstruct the diffusion of new environmental policy instruments. While the endorsement of regulatory instruments by international organizations or transnational advocacy networks often facilitates their diffusion, the instruments' characteristics determine the extent and speed by which regulatory instruments spread across countries. As regards policymakers' motivation for voluntarily adopting regulatory instruments, the paper argues that it cannot be exclusively explained by rational attempts to improve policy effectiveness. In addition, policy adoption is often motivated by concerns of legitimacy and

  19. Aspiration-based partner switching boosts cooperation in social dilemmas.

    Directory of Open Access Journals (Sweden)

    Zhi Li

    Full Text Available Most previous studies concerning linking dynamics often assumed that links pairing individuals should be identified and treated differently during topology adjusting procedure, in order to promote cooperation. A common assumption was that cooperators were expected to avoid being exploited by quickly breaking up relationships with defectors. Then the so-called prosocial links linking two cooperators (abbreviated as CC links hereafter would be much favored by evolution, whereby cooperation was promoted. However, we suggest that this is not always necessary. Here, we developed a minimal model in which an aspiration-based partner switching mechanism was embedded to regulate the evolution of cooperation in social dilemmas. Individuals adjusted social ties in a self-questioning manner in line with the learning theory. Less game information was involved during dynamic linking and all links were tackled anonymously irrespective of their types (i.e., CD links, DD links, or CC links. The main results indicate that cooperation flourishes for a broad range of parameters. The denser the underlying network, the more difficult the evolution of cooperation. More importantly, moderate aspirations do much better in promoting the evolution of altruistic behavior and for most cases there exists the optimal aspiration level that most benefits cooperation. Too strong or too weak selection intensity turns out to be pretty conducive to the evolution of cooperation in such a dynamical system.

  20. Impact of Co-Operative Learning Strategies in English

    Science.gov (United States)

    Singaravelu, G.

    2010-01-01

    The study illuminates the effectiveness of Co-operative Learning Strategies in learning English Grammar for the learners at secondary level. Cooperative Learning is particularly beneficial for any student learning as a second language. It promotes peer interaction, which helps the development of language and the learning of concepts with content.…

  1. Cooperative Learning: Review of Research and Practice

    Science.gov (United States)

    Gillies, Robyn M.

    2016-01-01

    Cooperative learning is widely recognized as a pedagogical practice that promotes socialization and learning among students from pre-school through to tertiary level and across different subject domains. It involves students working together to achieve common goals or complete group tasks--goals and tasks that they would be unable to complete by…

  2. When does gossip promote generosity? Indirect reciprocity under the shadow of the future

    NARCIS (Netherlands)

    Wu, J.; Balliet, D.P.; van Lange, P.A.M.

    2015-01-01

    Reputation through gossip is a key mechanism promoting cooperation. The present research proposes that gossip promotes cooperation when one anticipates future interdependence with the gossip recipient (Hypothesis 1), that this effect is more pronounced for proself, compared to prosocial, individuals

  3. Opening lecture: notes on cooperatives, partners and tax regulations

    Directory of Open Access Journals (Sweden)

    Tulio Rosembuj

    2005-12-01

    Full Text Available The promotion of cooperative society is not an empty and capricious concept. It has a definite basis in the Constitution (art.129.2, and its reflection in the tax legislation that applies to the member.

  4. Cooperative Engagement Capability (CEC)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-582 Cooperative Engagement Capability (CEC) As of FY 2017 President’s Budget Defense...Program Information Program Name Cooperative Engagement Capability (CEC) DoD Component Navy Joint Participants United States Marine Corps; United...dated June 16, 2004 CEC December 2015 SAR March 17, 2016 12:13:59 UNCLASSIFIED 5 Mission and Description Mission The Cooperative Engagement Capability

  5. Multilateral cooperation for power interconnection in Northeast Asia

    Science.gov (United States)

    Chudinova, Lyudmila; Podkovalnikov, Sergei; Trofimov, Ivan

    2018-01-01

    Considered is experience of electric power integration in different parts of the world with emphasis on bilateral/multilateral interstate structures intended for promotion and development of interstate power grids. Analysed are Northeast Asian intergovernmental structures providing bilateral energy and power cooperation between Russia and other countries of the region. Multilateral cooperation in the field is just emerging, but should play a key role in promotion and development of Northeast Asian power grid.

  6. Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation.

    Science.gov (United States)

    Araujo, Lindsey; Khim, Phillip; Mkhikian, Haik; Mortales, Christie-Lynn; Demetriou, Michael

    2017-01-06

    Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. This drives growth and pro-inflammatory T H 17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer.

  7. When cooperation begets cooperation: the role of key individuals in galvanizing support.

    Science.gov (United States)

    McAuliffe, Katherine; Wrangham, Richard; Glowacki, Luke; Russell, Andrew F

    2015-12-05

    Life abounds with examples of conspecifics actively cooperating to a common end, despite conflicts of interest being expected concerning how much each individual should contribute. Mathematical models typically find that such conflict can be resolved by partial-response strategies, leading investors to contribute relatively equitably. Using a case study approach, we show that such model expectations can be contradicted in at least four disparate contexts: (i) bi-parental care; (ii) cooperative breeding; (iii) cooperative hunting; and (iv) human cooperation. We highlight that: (a) marked variation in contributions is commonplace; and (b) individuals can often respond positively rather than negatively to the contributions of others. Existing models have surprisingly limited power in explaining these phenomena. Here, we propose that, although among-individual variation in cooperative contributions will be influenced by differential costs and benefits, there is likely to be a strong genetic or epigenetic component. We then suggest that selection can maintain high investors (key individuals) when their contributions promote support by increasing the benefits and/or reducing the costs for others. Our intentions are to raise awareness in--and provide testable hypotheses of--two of the most poorly understood, yet integral, questions regarding cooperative ventures: why do individuals vary in their contributions and when does cooperation beget cooperation? © 2015 The Author(s).

  8. Futures for energy cooperatives

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-01-01

    A listing of Federal agencies and programs with potential funding for community-scale cooperatives using conservation measures and solar technologies is presented in Section 1. Section 2 presents profiles of existing community energy cooperatives describing their location, history, membership, services, sources of finance and technical assistance. A condensed summary from a recent conference on Energy Cooperatives featuring notes on co-op members' experiences, problems, and opportunities is presented in Section 3. Section 4 lists contacts for additional information. A National Consumer Cooperative Bank Load Application is shown in the appendix.

  9. Synthetic Yeast Cooperation

    Science.gov (United States)

    Shou, Wenying; Burton, Justin

    2010-03-01

    Cooperation is wide-spread and has been postulated to drive major transitions in evolution. However, Darwinian selection favors ``cheaters'' that consume benefits without paying a fair cost. How did cooperation evolve against the threat of cheaters? To investigate the evolutionary trajectories of cooperation, we created a genetically tractable system that can be observed as it evolves from inception. The system consists of two engineered yeast strains -- a red-fluorescent strain that requires adenine and releases lysine and a yellow-fluorescent strain that requires lysine and releases adenine. Cells that consume but not supply metabolites would be cheaters. From the properties of two cooperating strains, we calculated and experimentally verified the minimal initial cell densities required for the viability of the cooperative system in the absence of exogenously added adenine and lysine. Strikingly, evolved cooperative systems were viable at 100-fold lower initial cell densities than their ancestors. We are investigating the nature and diversity of pro-cooperation changes, the dynamics of cooperator-cheater cocultures, and the effects of spatial environment on cooperation and cheating.

  10. Cooperative Station History Forms

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Various forms, photographs and correspondence documenting the history of Cooperative station instrumentation, location changes, inspections, and...

  11. Anti-regulatory T cells.

    Science.gov (United States)

    Andersen, Mads Hald

    2017-04-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells-termed anti-regulatory T cells (anti-Tregs)-that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells, including indoleamine 2,3-dioxygenase (IDO), tryptophan 2,6-dioxygenase (TDO), programmed death-ligand 1 (PD-L1), and forkhead box P3 (Foxp3). These proteins are highly expressed in professional antigen-presenting cells under various physiological conditions, such as inflammation and stress. Therefore, self-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles in immune homeostasis and their potential future clinical applications.

  12. Regulatory Myeloid Cells in Transplantation

    Science.gov (United States)

    Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

    2013-01-01

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

  13. UN MARCO PARA LA PROMOCIÓN DE COOPERATIVAS EN EL CONTEXTO DE PLANES DE DESARROLLO TERRITORIAL DE REGIONES DESFAVORECIDAS/A FRAME FOR THE PROMOTION OF CO-OPERATIVES IN THE CONTEXT OF PLANS OF TERRITORIAL DEVELOPMENT OF DISADVANTAGED REGIONS

    Directory of Open Access Journals (Sweden)

    Jorge COQUE MARTÍNEZ

    2007-05-01

    Full Text Available Este artículo propone un marco para orientar programas de promoción de cooperativas en regiones desfavorecidas, con base en la concepción de estas empresas como esencialmente participativas. Para ello, se han combinado elementos de Dirección Estratégica y de Investigación-Acción Participativa que permiten estructurar procesos de intervención según cuatro ámbitos fundamentales de análisis, decisión y actuación: (1 elección de las barreras limitantes del desarrollo empresarial cooperativo sobre las que se quiere incidir, tras diagnosticar la situación de las cooperativas objetivo de un determinado programa y la del entorno de éstas; (2 determinación de los instrumentos más adecuados de intervención, vinculados a la disminución de las barreras determinadas en el punto anterior; (3 selección de los actores de promoción y reparto de papeles, en función de sus capacidades y otros rasgos que determinan quiénes son más adecuados para aplicar determinados instrumentos; (4 adecuación continua del programa a medida que las cooperativas promovidas van recorriendo las diferentes etapas de su ciclo de vida./This article proposes a framework in order to guide co-operative promotion programs in disadvantaged regions, based on understanding these enterprises as essentially participatory. Strategic Management and Participatory Research-Action elements have been combined so that they allow to structure intervention processes according to four basic spheres of analysis, decision and action: (1 selecting the barriers that limit the co-operative entrepreneurial development to have a bearing on, after diagnosing the situation of co-operatives which are the object of a certain program and its environment; (2 determining the most adequate tools of intervention in order to reduce the barriers that had been determined in the former point; (3 selecting the agents of promotion, and sharing roles among them according to their capabilities and other

  14. Proto-cooperation

    DEFF Research Database (Denmark)

    Herbert-Read, James E; Romanczuk, Pawel; Krause, Stefan

    2016-01-01

    beneficial if the cost of attacking is high, and only then when waiting times are short. Our findings provide evidence that cooperative benefits can be realized through the facilitative effects of individuals' hunting actions without spatial coordination of attacks. Such 'proto-cooperation' may be the pre...

  15. Making Cooperative Learning Powerful

    Science.gov (United States)

    Slavin, Robert E.

    2014-01-01

    Just about everyone loves the "idea" of cooperative learning, children working productively and excitedly in groups, everyone getting along and enthusiastically helping one another learn. This article presents five strategies that teachers can use to get the greatest benefit possible from cooperative learning and ensure that…

  16. Can Altruism Hinder Cooperation?

    OpenAIRE

    Keisuke Nakao

    2008-01-01

    This note considers the effects of altruism on cooperation in the context of a repeated Prisoner's Dilemma. Altruism has two conflicting impacts on cooperation: One is to reduce the temptation for defection the other is to make the future punishment ineffective. The total effect of altruism hinges on the shape of players'' cost functions.

  17. Helping Children Cooperate

    Science.gov (United States)

    Pica, Rae

    2011-01-01

    There are occasions in life when the competitive process is appropriate. But when people consider the relationships in their lives--with friends, family members, coworkers, and the larger community--they realize the value of cooperation. When adults give children the chance to cooperate, to work together toward a solution or a common goal like…

  18. Scandinavian Cooperative Advantage

    DEFF Research Database (Denmark)

    Strand, Robert; Freeman, R. Edward

    2015-01-01

    . We conclude by endorsing the expression “Scandinavian cooperative advantage” in an effort to draw attention to the Scandinavian context and encourage the field of strategic management to shift its focus from achieving a competitive advantage toward achieving a cooperative advantage....

  19. A study on the enhancement of nuclear cooperation with African countries including utilization of radioisotope

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Maeng Ho; Oh, K. B; Lee, H. M. and others

    2005-05-15

    In this study, potential countries for nuclear cooperation in African region and possible cooperation areas were investigated between Korea and African countries including radioisotopes and more fields were also analysed in depth in order to suggest the recommendations for future cooperation to be considered as follows; First, current status and perspectives of demand and supply of energy and electricity in the African countries, use and development of nuclear energy and international nuclear cooperation were analyzed. Second, current status of nuclear cooperation between Korea and African countries were investigated as well as analysis of future cooperation potential and countries having potential for nuclear cooperation and possible cooperative activities were suggested considering potential of nuclear market in mid- and long term base and step by step. Third, desirable strategies and directions for the establishment and promotion of nuclear cooperation relations between Korea and African developing countries were suggested in order to develope cooperative relations in efficient and effective manners with African developing countries.

  20. A Trust-Based Model for Security Cooperating in Vehicular Cloud Computing

    Directory of Open Access Journals (Sweden)

    Zhipeng Tang

    2016-01-01

    Full Text Available VCC is a computing paradigm which consists of vehicles cooperating with each other to realize a lot of practical applications, such as delivering packages. Security cooperation is a fundamental research topic in Vehicular Cloud Computing (VCC. Because of the existence of malicious vehicles, the security cooperation has become a challenging issue in VCC. In this paper, a trust-based model for security cooperating, named DBTEC, is proposed to promote vehicles’ security cooperation in VCC. DBTEC combines the indirect trust estimation in Public board and the direct trust estimation in Private board to compute the trust value of vehicles when choosing cooperative partners; a trustworthy cooperation path generating scheme is proposed to ensure the safety of cooperation and increase the cooperation completion rates in VCC. Extensive experiments show that our scheme improves the overall cooperation completion rates by 6~7%.

  1. The Emergence of Relationship-based Cooperation

    Science.gov (United States)

    Xu, Bo; Wang, Jianwei

    2015-11-01

    This paper investigates the emergence of relationship-based cooperation by coupling two simple mechanisms into the model: tie strength based investment preference and homophily assumption. We construct the model by categorizing game participants into four types: prosocialists (players who prefers to invest in their intimate friends), antisocialists (players who prefer to invest in strangers), egoists (players who never cooperate) and altruists (players who cooperate indifferently with anyone). We show that the relationship-based cooperation (prosocialists) is favored throughout the evolution if we assume players of the same type have stronger ties than different ones. Moreover, we discover that strengthening the internal bonds within the strategic clusters further promotes the competitiveness of prosocialists and therefore facilitates the emergence of relationship-based cooperation in our proposed scenarios. The robustness of the model is also tested under different strategy updating rules and network structures. The results show that this argument is robust against the variations of initial conditions and therefore can be considered as a fundamental theoretical framework to study relationship-based cooperation in reality.

  2. Efficiency in Microfinance Cooperatives

    Directory of Open Access Journals (Sweden)

    HARTARSKA, Valentina

    2012-12-01

    Full Text Available In recognition of cooperatives’ contribution to the socio-economic well-being of their participants, the United Nations has declared 2012 as the International Year of Cooperatives. Microfinance cooperatives make a large part of the microfinance industry. We study efficiency of microfinance cooperatives and provide estimates of the optimal size of such organizations. We employ the classical efficiency analysis consisting of estimating a system of equations and identify the optimal size of microfinance cooperatives in terms of their number of clients (outreach efficiency, as well as dollar value of lending and deposits (sustainability. We find that microfinance cooperatives have increasing returns to scale which means that the vast majority can lower cost if they become larger. We calculate that the optimal size is around $100 million in lending and half of that in deposits. We find less robust estimates in terms of reaching many clients with a range from 40,000 to 180,000 borrowers.

  3. Cooperation in Construction:

    DEFF Research Database (Denmark)

    Vogelius, Peter; Storgaard, Kresten

    2016-01-01

    The study presents a building project executed by a major Danish construction company, where cooperation and its staging were essential for achieving high productivity and competitiveness. The form of this cooperation is the main theme for the article. The contractor actively changed...... the communication and sociological values of the actors involved and saw it as essential for their way of cooperating. The cooperation included and combined elements of traditional industrial building production, with concepts and initiatives that had to be understood by means of sociological analysis. Tentatively...... the companies in the case can be understood as possessing a social capital which is enforced and united by initiatives of the main contractor. The social capital was built up and maintained through the actual constitution of cooperation already in the initial phase of bidding before the building process...

  4. Worker cooperatives in Mexico and Tax reforms

    Directory of Open Access Journals (Sweden)

    Martha E. Izquierdo

    2016-12-01

    Full Text Available Because of the economic problems currently facing our country, it becomes increasingly important the creation of cooperative enterprises as an economic alternative, for its ability to create jobs and thereby generating wealth and development. However with fiscal reforms that the Federal government has implemented since 2014, eliminating a number of tax incentives, for some sectors including cooperative societies of production as necessary to address the problems that exist, far from promoting job creation and wealth, they annihilate them even they trumpet they have a social character, it turns out the opposite.Received : 09.05.2016Accepted: 05.09.2016

  5. Concepts and Practices of Cooperative Security

    DEFF Research Database (Denmark)

    Keating, Vincent; Wheeler, Nicholas J

    2013-01-01

    This chapter considers how the security dilemma can be overcome in ways that promote cooperation and even trust, mitigating or transcending the international uncertainty that can otherwise inhibit interstate cooperation. It argues that there are two mechanisms to create the trust necessary...... for the development of a security community, Charles Osgood's GRIT strategy and a unilateral 'leap of trust.' Both of these, however, initially require elites to develop security dilemma sensibility. The long-term stability of security communities is fundamentally linked to the presence of embedded trust among...

  6. Globalization and its Impact on Cooperatives – A Case of Oromiya ...

    African Journals Online (AJOL)

    Present research was designed to find the contribution of globalization to cooperative organizations in Oromiya region, Ethiopia. 152 employees from Oromiya regional cooperative promotion office working in cooperative organizations in the 17 zones of Oromiya region joined Wollega University for their upgrading ...

  7. Educational Cooperation between Thailand and Cambodia: Outcomes on Human Development, International Understanding and Future Prospect

    Science.gov (United States)

    Kijtorntham, Wichuda; Ruangdej, Phumjit; Saisuwan, Chatchanog

    2015-01-01

    Thailand and Cambodia set up educational cooperation since 1996, before signed a Memorandum of Understanding on Cooperation in the Promotion of Education in 2003. This research aimed to investigate outcomes of educational cooperation projects on Cambodia human development and international understanding, process of participatory learning and…

  8. Versatility of cooperative transcriptional activation: a thermodynamical modeling analysis for greater-than-additive and less-than-additive effects.

    Directory of Open Access Journals (Sweden)

    Till D Frank

    Full Text Available We derive a statistical model of transcriptional activation using equilibrium thermodynamics of chemical reactions. We examine to what extent this statistical model predicts synergy effects of cooperative activation of gene expression. We determine parameter domains in which greater-than-additive and less-than-additive effects are predicted for cooperative regulation by two activators. We show that the statistical approach can be used to identify different causes of synergistic greater-than-additive effects: nonlinearities of the thermostatistical transcriptional machinery and three-body interactions between RNA polymerase and two activators. In particular, our model-based analysis suggests that at low transcription factor concentrations cooperative activation cannot yield synergistic greater-than-additive effects, i.e., DNA transcription can only exhibit less-than-additive effects. Accordingly, transcriptional activity turns from synergistic greater-than-additive responses at relatively high transcription factor concentrations into less-than-additive responses at relatively low concentrations. In addition, two types of re-entrant phenomena are predicted. First, our analysis predicts that under particular circumstances transcriptional activity will feature a sequence of less-than-additive, greater-than-additive, and eventually less-than-additive effects when for fixed activator concentrations the regulatory impact of activators on the binding of RNA polymerase to the promoter increases from weak, to moderate, to strong. Second, for appropriate promoter conditions when activator concentrations are increased then the aforementioned re-entrant sequence of less-than-additive, greater-than-additive, and less-than-additive effects is predicted as well. Finally, our model-based analysis suggests that even for weak activators that individually induce only negligible increases in promoter activity, promoter activity can exhibit greater

  9. The Cooperative Agricultural Pest Survey Program (CAPS): scientific support to optimize a national program

    Science.gov (United States)

    Lisa D. Jackson; Daniel A. Fieselmann

    2011-01-01

    The mission of the Cooperative Agricultural Pest Survey (CAPS) program is to provide a survey profile of exotic plant pests in the United States deemed to be of regulatory significance to USDA Animal and Plant Health Inspection Service (APHIS), Plant Protection and Quarantine (PPQ), State Departments of Agriculture, tribal governments, and cooperators by confirming the...

  10. Regulation during Cooperative and Collaborative Learning: A Theory-Based Review of Terms and Concepts

    Science.gov (United States)

    Schoor, Cornelia; Narciss, Susanne; Körndle, Hermann

    2015-01-01

    This article reviews the terms and concepts that have been used for describing regulation of learning during cooperative and collaborative learning and suggests differentiating them on the basis of which parts of a regulatory feedback loop model are being shared. During cooperative and collaborative learning, not only self-regulation but also the…

  11. 77 FR 28873 - Nuvista Light and Electric Cooperative, Inc.; Notice of Preliminary Permit Application Accepted...

    Science.gov (United States)

    2012-05-16

    ... containing two vertical Francis turbine/generator units rated for 6.7 megawatts (MW) each, for a total... Energy Regulatory Commission Nuvista Light and Electric Cooperative, Inc.; Notice of Preliminary Permit... Competing Applications On March 2, 2012, Nuvista Light and Electric Cooperative, Inc., filed an application...

  12. 77 FR 20019 - Nuvista Light and Electric Cooperative, Inc.; Notice of Preliminary Permit Application Accepted...

    Science.gov (United States)

    2012-04-03

    ... vertical Francis turbine/generator units rated for 6.7 megawatts (MW) each, for a total installed capacity... Energy Regulatory Commission Nuvista Light and Electric Cooperative, Inc.; Notice of Preliminary Permit... March 2, 2012, Nuvista Light and Electric Cooperative, Inc., filed an application for a preliminary...

  13. Japan`s international cooperation programs on seismic safety of nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Sanada, Akira [Agency of Natural Resources and Energy, Tokyo (Japan)

    1997-03-01

    MITI is promoting many international cooperation programs on nuclear safety area. The seismic safety of nuclear power plants (NPPs) is a one of most important cooperation areas. Experts from MITI and related organization join the multilateral cooperation programs carried out by international organization such as IAEA, OECD/NEA etc. MITI is also promoting bilateral cooperation programs such as information exchange meetings, training programs and seminars on nuclear safety with several countries. Concerning to the cooperation programs on seismic safety of NPPs such as information exchange and training, MITI shall continue and expand these programs. (J.P.N.)

  14. Scientific-technical cooperation with foreign (esp. Europe and INSC partner countries) nuclear regulatory authorities and their technical support organizations in the fields of nuclear safety of operating nuclear power plants and on the concept evaluation of generation 3+ plants. Final report; Wissenschaftlich-Technische Zusammenarbeit (WTZ) mit auslaendischen (insbesondere in Europa und INSC-Partnerstaaten) atomrechtlichen Behoerden und deren Sachverstaendigenorganisationen zur nuklearen Sicherheit in Betrieb befindlicher Kernkraftwerke und zur Konzeptbewertung von Generation-3+-Anlagen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Holger

    2016-09-15

    The BMUB/BfS-Project 3614I01512 forms the frame of the GRS for the scientific-technical cooperation with Technical Support Organisations and Nuclear Regulatory Authorities in the field of nuclear safety in operating NPPs and for the concept evaluation of generation 3{sup +} plants in Europe and INSC Partner Countries. In the present final project report results are described which were gained within the project duration 15.10.2014 up to the 30.09.2016 in the following working packages: Investigations following the catastrophe of Fukushima Daiichi, Evaluation of selected National Action Plans, DBA and severe accident analyses for NPP with PWR (WWER-440, WWER-1000), cooperation with INSC partner countries on DBA, BDBA and severe accident analyses for WWER plants of generation 3{sup +} and building NRA and safety evaluation capacities and decommissioning of nuclear facilities and disposal of radioactive waste. The results are preceded by an outline on the activities related to the project management and to the planning of the bilateral work.

  15. Contagion of Cooperation in Static and Fluid Social Networks.

    Science.gov (United States)

    Jordan, Jillian J; Rand, David G; Arbesman, Samuel; Fowler, James H; Christakis, Nicholas A

    2013-01-01

    Cooperation is essential for successful human societies. Thus, understanding how cooperative and selfish behaviors spread from person to person is a topic of theoretical and practical importance. Previous laboratory experiments provide clear evidence of social contagion in the domain of cooperation, both in fixed networks and in randomly shuffled networks, but leave open the possibility of asymmetries in the spread of cooperative and selfish behaviors. Additionally, many real human interaction structures are dynamic: we often have control over whom we interact with. Dynamic networks may differ importantly in the goals and strategic considerations they promote, and thus the question of how cooperative and selfish behaviors spread in dynamic networks remains open. Here, we address these questions with data from a social dilemma laboratory experiment. We measure the contagion of both cooperative and selfish behavior over time across three different network structures that vary in the extent to which they afford individuals control over their network ties. We find that in relatively fixed networks, both cooperative and selfish behaviors are contagious. In contrast, in more dynamic networks, selfish behavior is contagious, but cooperative behavior is not: subjects are fairly likely to switch to cooperation regardless of the behavior of their neighbors. We hypothesize that this insensitivity to the behavior of neighbors in dynamic networks is the result of subjects' desire to attract new cooperative partners: even if many of one's current neighbors are defectors, it may still make sense to switch to cooperation. We further hypothesize that selfishness remains contagious in dynamic networks because of the well-documented willingness of cooperators to retaliate against selfishness, even when doing so is costly. These results shed light on the contagion of cooperative behavior in fixed and fluid networks, and have implications for influence-based interventions aiming at

  16. What drives cooperative breeding?

    Directory of Open Access Journals (Sweden)

    Walter D Koenig

    2017-06-01

    Full Text Available Cooperative breeding, in which more than a pair of conspecifics cooperate to raise young at a single nest or brood, is widespread among vertebrates but highly variable in its geographic distribution. Particularly vexing has been identifying the ecological correlates of this phenomenon, which has been suggested to be favored in populations inhabiting both relatively stable, productive environments and in populations living under highly variable and unpredictable conditions. Griesser et al. provide a novel approach to this problem, performing a phylogenetic analysis indicating that family living is an intermediate step between nonsocial and cooperative breeding birds. They then examine the ecological and climatic conditions associated with these different social systems, concluding that cooperative breeding emerges when family living is favored in highly productive environments, followed secondarily by selection for cooperative breeding when environmental conditions deteriorate and within-year variability increases. Combined with recent work addressing the fitness consequences of cooperative breeding, Griesser et al.'s contribution stands to move the field forward by demonstrating that the evolution of complex adaptations such as cooperative breeding may only be understood when each of the steps leading to it are identified and carefully integrated.

  17. Standardization of SOPs to Evaluations: Impacts on Regulatory Decisions using Learning and Memory as Case Studies

    Science.gov (United States)

    In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential, particularly for non­ standard assays and variable endpoints. Because there is flexibility in the selection of ...

  18. 7 CFR 4290.585 - Voluntary decrease in RBIC's Regulatory Capital.

    Science.gov (United States)

    2010-01-01

    ... BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Managing the Operations of a RBIC Voluntary Decrease in Regulatory...

  19. Cognitive Load and Cooperation

    DEFF Research Database (Denmark)

    Døssing, Felix Sebastian; Piovesan, Marco; Wengström, Erik Roland

    2017-01-01

    We study the effect of intuitive and reflective processes on cooperation using cognitive load. Compared with time constraint, which has been used in the previous literature, cognitive load is a more direct way to block reflective processes, and thus a more suitable way to study the link between...... intuition and cooperation. Using a repeated public goods game, we study the effect of different levels of cognitive load on contributions. We show that a higher cognitive load increases the initial level of cooperation. In particular, subjects are significantly less likely to fully free ride under high...... cognitive load....

  20. ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH

    Science.gov (United States)

    ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH, designed to stimulate dialogue on ethical and regulatory issues in cancer research and promote awareness of developing policies and best practices.

  1. To craft or not to craft : The relationships between regulatory focus, job crafting and work outcomes

    NARCIS (Netherlands)

    Brenninkmeijer, Veerle|info:eu-repo/dai/nl/182274551; Hekkert-Koning, Marleen

    2015-01-01

    Purpose – The purpose of this paper is to examine relationships between regulatory focus, job crafting, work engagement and perceived employability. Regulatory focus theory distinguishes between promotion-focused individuals, who strive for growth and development, and preventionfocussed individuals,

  2. The Rural Cooperative in China under the Governance of the Christ Ethic Value

    Directory of Open Access Journals (Sweden)

    Xiliang Wu

    2014-04-01

    Full Text Available Based on the analysis on the basic information, problems and characters of rural cooperative in China, the paper finds that the cooperative governance by the blood, institution should be changed into the governance by civil ethic. We compare the relation between Christ ethic and the rural cooperative in China and find the close relation between them. The cooperation, equality and devotion in cooperatives are also shown in Christ. With the case of the cooperatives found by Chinese Christians, we also find that the belief in China should be of freedom, the traditional ethic should be innovated and the religions could promote the daily public good affairs without the political intervention.

  3. Ordering structured populations in multiplayer cooperation games

    Science.gov (United States)

    Peña, Jorge; Wu, Bin; Traulsen, Arne

    2016-01-01

    Spatial structure greatly affects the evolution of cooperation. While in two-player games the condition for cooperation to evolve depends on a single structure coefficient, in multiplayer games the condition might depend on several structure coefficients, making it difficult to compare different population structures. We propose a solution to this issue by introducing two simple ways of ordering population structures: the containment order and the volume order. If population structure is greater than population structure in the containment or the volume order, then can be considered a stronger promoter of cooperation. We provide conditions for establishing the containment order, give general results on the volume order, and illustrate our theory by comparing different models of spatial games and associated update rules. Our results hold for a large class of population structures and can be easily applied to specific cases once the structure coefficients have been calculated or estimated. PMID:26819335

  4. Cooperative endeavors: A case study of success

    Energy Technology Data Exchange (ETDEWEB)

    Baker, J. [Ford Motor Co., Dearborn, MI (United States)

    1997-12-31

    Partnerships and cooperative agreements abound in the environmental arena today. This paper briefly highlights the collaborative approach used by the International Cooperative for Ozone Layer Protection (ICOLP). ICOLP has helped international members and non-members to eliminate most of the ozone-depleting solvents from manufacturing processes through the exchange of technical information in a non-proprietary manner. By using alternatives, companies and governments have realized savings in the multiple millions of dollars. Advantages of participating in cooperative environmental partnerships may include: (1) improved access and exchange of information, (2) cost minimization, (3) promotion and facilitation of business opportunities, (4) improved dialogue between groups, (5) coordinated approach to complex issues, and (6) technology development and transfer opportunities.

  5. Ordering structured populations in multiplayer cooperation games.

    Science.gov (United States)

    Peña, Jorge; Wu, Bin; Traulsen, Arne

    2016-01-01

    Spatial structure greatly affects the evolution of cooperation. While in two-player games the condition for cooperation to evolve depends on a single structure coefficient, in multiplayer games the condition might depend on several structure coefficients, making it difficult to compare different population structures. We propose a solution to this issue by introducing two simple ways of ordering population structures: the containment order and the volume order. If population structure S1 is greater than population structure S1 in the containment or the volume order, then S1 can be considered a stronger promoter of cooperation. We provide conditions for establishing the containment order, give general results on the volume order, and illustrate our theory by comparing different models of spatial games and associated update rules. Our results hold for a large class of population structures and can be easily applied to specific cases once the structure coefficients have been calculated or estimated. © 2016 The Authors.

  6. BRNI: Modular analysis of transcriptional regulatory programs

    Directory of Open Access Journals (Sweden)

    Nachman Iftach

    2009-05-01

    Full Text Available Abstract Background Transcriptional responses often consist of regulatory modules – sets of genes with a shared expression pattern that are controlled by the same regulatory mechanisms. Previous methods allow dissecting regulatory modules from genomics data, such as expression profiles, protein-DNA binding, and promoter sequences. In cases where physical protein-DNA data are lacking, such methods are essential for the analysis of the underlying regulatory program. Results Here, we present a novel approach for the analysis of modular regulatory programs. Our method – Biochemical Regulatory Network Inference (BRNI – is based on an algorithm that learns from expression data a biochemically-motivated regulatory program. It describes the expression profiles of gene modules consisting of hundreds of genes using a small number of regulators and affinity parameters. We developed an ensemble learning algorithm that ensures the robustness of the learned model. We then use the topology of the learned regulatory program to guide the discovery of a library of cis-regulatory motifs, and determined the motif compositions associated with each module. We test our method on the cell cycle regulatory program of the fission yeast. We discovered 16 coherent modules, covering diverse processes from cell division to metabolism and associated them with 18 learned regulatory elements, including both known cell-cycle regulatory elements (MCB, Ace2, PCB, ACCCT box and novel ones, some of which are associated with G2 modules. We integrate the regulatory relations from the expression- and motif-based models into a single network, highlighting specific topologies that result in distinct dynamics of gene expression in the fission yeast cell cycle. Conclusion Our approach provides a biologically-driven, principled way for deconstructing a set of genes into meaningful transcriptional modules and identifying their associated cis-regulatory programs. Our analysis sheds

  7. Cooperative Extension Answers the Call to Action to Support Breastfeeding

    Science.gov (United States)

    Brill, Michelle F.

    2016-01-01

    Extension has many opportunities to promote breastfeeding, one of the most highly effective preventive measures a mother can take to protect the health of her infant and herself. This article describes how and why Cooperative Extension can and should partner with federal and state efforts to promote breastfeeding. Members of Rutgers' Family and…

  8. Globalization and economic cooperation

    Directory of Open Access Journals (Sweden)

    Javier Divar

    2006-12-01

    Full Text Available Economic globalization is nothing, really, that the universality of capitalism. Not globalized culture, and economic participation, and human rights, ... has only globalized market. We must react by substituting those materialistic values with cooperative economy.

  9. Solar cooperatives; Genosse Sonne

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Dierk

    2010-06-15

    Not a boom but a trend: Increasingly, solar power plants and other renewables-based systems are financed by cooperatives. This organizational structure requires long-term strategies and some idealism. (orig.)

  10. Cooperative Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2009-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a novel optimization algorithm based on the social foraging behavior of E. coli bacteria. This paper presents a variation on the original BFO algorithm, namely, the Cooperative Bacterial Foraging Optimization (CBFO, which significantly improve the original BFO in solving complex optimization problems. This significant improvement is achieved by applying two cooperative approaches to the original BFO, namely, the serial heterogeneous cooperation on the implicit space decomposition level and the serial heterogeneous cooperation on the hybrid space decomposition level. The experiments compare the performance of two CBFO variants with the original BFO, the standard PSO and a real-coded GA on four widely used benchmark functions. The new method shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  11. On Cooper's Nonparametric Test.

    Science.gov (United States)

    Schmeidler, James

    1978-01-01

    The basic assumption of Cooper's nonparametric test for trend (EJ 125 069) is questioned. It is contended that the proper assumption alters the distribution of the statistic and reduces its usefulness. (JKS)

  12. Cooperation among microorganisms.

    OpenAIRE

    Wingreen, Ned S.; Levin, Simon A

    2006-01-01

    Understanding cooperation among microorganisms presents conceptual and mathematical challenges at the interface of evolutionary biology and the theory of emergent properties of independent agents, two of the most exciting areas in modern mathematical biology.

  13. Cooperative processing data bases

    Science.gov (United States)

    Hasta, Juzar

    1991-01-01

    Cooperative processing for the 1990's using client-server technology is addressed. The main theme is concepts of downsizing from mainframes and minicomputers to workstations on a local area network (LAN). This document is presented in view graph form.

  14. Regional National Cooperative Observer

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA publication dedicated to issues, news and recognition of observers in the National Weather Service Cooperative Observer program. Issues published regionally...

  15. Cooperative Hurricane Network Obs

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Observations from the Cooperative Hurricane Reporting Network (CHURN), a special network of stations that provided observations when tropical cyclones approached the...

  16. Cooperative Learning Strategies.

    Science.gov (United States)

    Pratt, Sandra

    2003-01-01

    Describes the effectiveness of cooperative learning on discipline problems, interdependence between students, and teacher-student interactions. Explains how to group students and introduces a laboratory activity on covalent and ionic bonds. (YDS)

  17. Cooperative Weather Observations

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Monthly logs include a daily account of temperature extremes and precipitation, along with snow data at some locations. U.S. Cooperative Observer Program (COOP)...

  18. Cooperating mobile robots

    Science.gov (United States)

    Harrington, John J.; Eskridge, Steven E.; Hurtado, John E.; Byrne, Raymond H.

    2004-02-03

    A miniature mobile robot provides a relatively inexpensive mobile robot. A mobile robot for searching an area provides a way for multiple mobile robots in cooperating teams. A robotic system with a team of mobile robots communicating information among each other provides a way to locate a source in cooperation. A mobile robot with a sensor, a communication system, and a processor, provides a way to execute a strategy for searching an area.

  19. From cooperation to globalization

    OpenAIRE

    Gabriela UNGUREANU

    2010-01-01

    Globalization is seen as a consequence of cross-border business. This complex and irreversible process can be seen as an extension of capitalist relations of production or increased interdependence in the economic system. Globalization has given rise to more and more fields of activity worldwide. To meet the challenges of business globalization, many companies form strategic alliances, cooperate or merge with other companies. Cooperation is seen by many companies as an alternative path to suc...

  20. Cooperative Team Networks

    Science.gov (United States)

    2016-06-01

    framework and motivation for this mathematical formalization for cooperative principles. The insight was the quantification of an individual’s...theories need to be formalized so they can better inform mathematical and computational models. The interest is clearly there. This conference was meant...this mathematical formalization for cooperative principles. The insight was the quantification of an individual’s contribution to the group effort

  1. Game theory in communication networks cooperative resolution of interactive networking scenarios

    CERN Document Server

    Antoniou, Josephina

    2012-01-01

    A mathematical tool for scientists and researchers who work with computer and communication networks, Game Theory in Communication Networks: Cooperative Resolution of Interactive Networking Scenarios addresses the question of how to promote cooperative behavior in interactive situations between heterogeneous entities in communication networking scenarios. It explores network design and management from a theoretical perspective, using game theory and graph theory to analyze strategic situations and demonstrate profitable behaviors of the cooperative entities. The book promotes the use of Game T

  2. Imitating winner or sympathizing loser? Quadratic effects on cooperative behavior in prisoners' dilemma games

    Science.gov (United States)

    Lu, Peng

    2015-10-01

    Cooperation is vital in human societies and therefore is widely investigated in the evolutionary game theory. Varieties of mechanisms have been proposed to overcome temptation and promote cooperation. Existing studies usually believe that agents are rational, but irrationalism such as emotions and feelings matters as well. Winner and loser are defined by their payoffs. In addition to admiring and imitating winners, the mechanism of sympathizing and imitating losers is introduced into the model as an alternative action rule, and each one plays the prisoners' dilemma game with eight neighbors under the influence of both irrationalism and rationalism. Rationalism refers to imitating winner to get highest payoff, and irrationalism means that people sympathize and adopt the actions of losers. As it is widely recognized that temptation reduces cooperation, this study focuses on the effect of sympathy on cooperation within a certain group or society. If it overcomes temptation that leads to defection, sympathy will be a powerful mechanism to promote cooperative behavior. Simulation results indicate that sympathy and temptation shares similar quadratic relationships with cooperation. Both sympathy and temptation undermine cooperation below their thresholds, and they both promote cooperation above their thresholds. Temptation not only reduces cooperation but also promote it as temptation goes beyond the threshold. Although sympathy is a good merit or human nature that is beneficial to society, a crisis or collapse of cooperation is inevitable when the sympathy propensity is relatively smaller. After cooperation reaches a minimal bottom, it then rises increasingly and dramatically, which brings a much brighter future of the society.

  3. FY 1998 annual summary report on International Clean Energy Network Using Hydrogen Conversion (WE-NET) system technology. Subtask 2. Examination and promotion of measures to obtain international understanding and cooperation; 1998 nendo seika hokokusho. Suiso riyo kokusai clean energy system gijutsu (WE-NET) subtask 2 (kokusai kyoryoku shuishin no tame no chosa kento)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    Described herein are the results of examination and promotion of measures to obtain international understanding and cooperation, and examination and development of measures to promote international exchange of technical information, conducted in the FY 1998 continuously from the previous year, with the object to realize the International Clean Energy Network Using Hydrogen Conversion (WE-NET) project. In the FY 1998, the English version of the 1997 annual summary report was distributed to a total of about 150 overseas organizations. The WE-NET project activities were presented to the 12th World Hydrogen Energy Conference, International Joint Power Generation Conference held in 1998 by American Society of Mechanical Engineers, and 2nd International Symposium on Advanced Energy Conversion Systems and Related Technologies. For the examination and development of measures to promote international exchange of technical information, the contracting party of Japan for the Hydrogen Implementation Agreement with IEA has been shifted from the government of Japan to NEDO. NEDO has been representing Japan for various workshops on the tasks. The hydrogen projects conducted by Germany and USA were also surveyed. The WE-NET project homepage was opened in June, 1998. (NEDO)

  4. International cooperation in water resources

    Science.gov (United States)

    Jones, J.R.; Beall, R.M.; Giusti, E.V.

    1979-01-01

    Advancements in hydrology proceeded slowly until the late 1800's when new ventures created a surge of interest and accomplishment. Progress waned again until the middle 20th century when an International Hydrological Decade was conceived, eventually receiving wide multinational support from governmental agencies and nongovernmental institutions. Organized by UNESCO, the Decade program was launched January 1, 1965. Participation included 107 nations, six United Nations agencies, and more than a dozen international scientific organizations. The initial program emphasized scientific research, and international cooperation; the second half of the Decade, emphasized technical assistance and technology transfer, largerly through education, training and demonstration. The success of the Decade led to the establishment of the International Hydrological Program, again under the aegis of UNESCO, to continue the work of the Decade indefinitely. The five major program activities, now involving about 90 countries and several international organizations, include: the scientific program, the promotion of education and training, the enhancement of information exchange, support of technical assistance, and the enlargement of regional cooperation. A significant amount of activity related to hydrological data networks and forecasting is carried on in an Operational Hydrology Programme by the WMO, chiefly through its Commission for Hydrology. Other international governmental organizations with a strong interest in water include the UN, the UN Development Programme, the FAO, the WHO, the International Atomic Energy Agency, the UN Environment Programme, the International Standardization Organization, and developmental institutions such as the World Bank. The specialized interests of researchers outside of the governmental structure, are met through association in various scientific and technical organizations which are world wide in scope and membership. Notwithstanding a sometimes

  5. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  6. Personal Trust Increases Cooperation beyond General Trust

    Science.gov (United States)

    Acedo-Carmona, Cristina; Gomila, Antoni

    2014-01-01

    In this paper we present a new methodology which, while allowing for anonymous interaction, it also makes possible to compare decisions of cooperating or defecting when playing games within a group, according to whether or not players personally trust each other. The design thus goes beyond standard approaches to the role of trust in fostering cooperation, which is restricted to general trust. It also allows considering the role of the topology of the social network involved may play in the level of cooperation found. The results of this work support the idea that personal trust promotes cooperation beyond the level of general trust. We also found that this effect carries over to the whole group, making it more cohesive, but that higher levels of cohesion rely on a particular topology. As a conclusion, we hypothesize that personal trust is a psychological mechanism evolved to make human social life possible in the small groups our ancestors lived in, and that this mechanism persists and plays a role in sustaining cooperation and social cohesion. PMID:25144539

  7. Cooperative monitoring and its role in regional security

    Energy Technology Data Exchange (ETDEWEB)

    Biringer, K.; Olsen, J.; Lincoln, R.; Wehling, F. [and others

    1997-03-01

    Cooperative monitoring systems can play an important part in promoting the implementation of regional cooperative security agreements. These agreements advance the national security interests of the United States in a post Cold War environment. Regional issues as widely varying as nuclear nonproliferation, trade and environmental pollution can be the source of tensions which may escalate to armed conflict which could have global implications. The Office of National Security Policy Analysis at the US Department of Energy (DOE) has an interest in seeking ways to promote regional cooperation that can reduce the threats posed by regional conflict. DOE technologies and technical expertise can contribute to developing solutions to a wide variety of these international problems. Much of this DOE expertise has been developed in support of the US nuclear weapons and arms control missions. It is now being made available to other agencies and foreign governments in their search for regional security and cooperation. This report presents two examples of interest to DOE in which monitoring technologies could be employed to promote cooperation through experimentation. The two scenarios include nuclear transparency in Northeast Asia and environmental restoration in the Black Sea. Both offer the potential for the use of technology to promote regional cooperation. The issues associated with both of these monitoring applications are presented along with examples of appropriate monitoring technologies, potential experiments and potential DOE contributions to the scenarios.

  8. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Regulatory Review Presidential Documents Other Presidential Documents Memorandum of January 30, 2009 Regulatory Review Memorandum for the Heads of Executive Departments and Agencies For well over two decades, the Office of Information and Regulatory Affairs (OIRA) at...

  9. Reducing the Effect of Stereotype Threat: The Role of Coaction Contexts and Regulatory Fit

    Science.gov (United States)

    Wen, Fangfang; Zuo, Bin; Wu, Yang; Dong, Xuanhao; Wang, Wei

    2016-01-01

    Two experiments examined the effects of competition and cooperation contexts, as well as regulatory fit, on reducing the negative influence of stereotype threat. Experiment 1 demonstrated that in high stereotype threat conditions, participants in the cooperation context scored significantly higher on a math test than those in the competition…

  10. Oral anti-CD3 immunotherapy for HCV-nonresponders is safe, promotes regulatory T cells and decreases viral load and liver enzyme levels: results of a phase-2a placebo-controlled trial.

    Science.gov (United States)

    Halota, W; Ferenci, P; Kozielewicz, D; Dybowska, D; Lisovoder, N; Samira, S; Shalit, I; Ellis, R; Ilan, Y

    2015-08-01

    Orally administered anti-CD3 antibodies are biologically active in the gut through induction of regulatory T cells, exert an immune-modulatory effect, and alleviate insulin resistance and liver damage in patients with NASH. To determine the safety of oral anti-CD3 monoclonal antibody (MAb) immunotherapy in chronic HCV patients with associated immune dysfunction. Four groups (n = 9) of chronic HCV patients who were nonresponders to interferon plus ribavirin therapy received oral placebo (group A) or anti-CD3 MAb at one of three dosage levels for 30 days. Patients were followed for safety parameters and serum levels of liver enzymes, virus, cytokines and regulatory T cells. Oral anti-CD3 immunotherapy was safe and well tolerated; no treatment-related adverse events were noted. The following improvements were noted relative to pretreatment levels: HCV viral load and AST and ALT levels decreased in the low- and high-dose groups following 30 days of therapy. In two of the treated groups, an increase in regulatory T cells (CD4(+) CD25(+) ) was noted. The positive effects were somewhat more apparent in subjects with initially elevated liver enzyme levels. Oral anti-CD3 MAb immunotherapy for nonresponder HCV patients was safe and well tolerated. Trends and statistically significant improvements were observed as reductions in viral load and liver enzyme levels, along with an increase in regulatory T-cell levels. These data support a role for the immune system in the pathogenesis of HCV infection and suggest that this immunotherapy is worthy of evaluation in combination with HCV antiviral drugs. © 2014 John Wiley & Sons Ltd.

  11. Protein extract of ultraviolet-irradiated human skin keratinocytes promote the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and 4.

    Science.gov (United States)

    Wang, Xiao-Yong; Tao, Cheng-Jun; Wu, Qiao-Yun; Yuan, Cheng-Da

    2013-02-01

    In this study, we investigated whether the protein extract of ultraviolet-irradiated human skin keratinocytes can activate Toll-like receptor 2 and Toll-like receptor 4 of Langerhans cells and induce the downstream gene expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3. The protein expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells and the protein expression of HSP60, HSP70 and β-defensin 2 in keratinocytes were examined using Western blot analysis. Langerhans cells were pretreated with or without Toll-like receptor 2 and Toll-like receptor 4 siRNA. We found that the protein extract of ultraviolet-irradiated keratinocytes upregulated the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and Toll-like receptor 4. We also found that ultraviolet radiation upregulated the expression HSP60, HSP70 and β-defensin 2 in keratinocytes. Our previous study demonstrated that ultraviolet radiation upregulated Toll-like receptor 2 and Toll-like receptor 4 expression in Langerhans cells. Ultraviolet radiation also upregulated mitogen-activated protein kinases and nuclear factor-κB/p65 expression via Toll-like receptor 2 and Toll-like receptor 4, and upregulated interferon regulatory factor-3 expression partially via Toll-like receptor 4. So we conclude that ultraviolet radiation can directly or indirectly activate keratinocytes to induce endogenous ligands which stimulate Toll-like receptor 2- or Toll-like receptor 4-dependent signaling cascade in Langerhans cells, sequentially influence innate and adaptive immune responses. © 2013 John Wiley & Sons A/S.

  12. Does intuition cause cooperation?

    Directory of Open Access Journals (Sweden)

    Peter P J L Verkoeijen

    Full Text Available Recently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more money to a common project when they had to decide quickly (i.e., a decision based on intuition than when they were instructed to reflect and decide slowly. This intuitive-cooperation effect is of high scientific and practical importance because it argues against a central assumption of traditional economic and evolutionary models. The first experiment of present study was set up to examine the generality of the intuitive-cooperation effect and to further validate the experimental task producing the effect. In Experiment 1, we investigated Amazon Mechanical Turk (AMT workers' contributions to a 4-player public goods game with a marginal return of 0.5 while we manipulated the knowledge about the other players' contribution to the public goods game (contribution known vs. contribution unknown, the identity of the other players (humans vs. computers randomly generating contributions and the time constraint (time pressure/intuition vs. forced delay/reflection. However, the results of Experiment 1 failed to reveal an intuitive-cooperation effect. Furthermore, four subsequent direct replications attempts with AMT workers (Experiments 2a, 2b, 2c and Experiment 3, which was conducted with naïve/inexperienced participants also failed to demonstrate intuitive-cooperation effects. Taken together, the results of the present study could not corroborate the idea that people are intuitively cooperative, hence suggesting that the theoretical relationship between intuition and cooperation should be further scrutinized.

  13. Evaluation of the Development pf Various Forms of Agriculture Cooperation in the Republic of Kazakhstan

    Directory of Open Access Journals (Sweden)

    Akimbekova Galiya

    2017-05-01

    Full Text Available The article analyzes the current situation in the agricultural complex of the Republic of Kazakhstan, the necessity of combining small farms in the cooperative structure, evaluation of existing forms of cooperatives in agriculture are substantiated (production cooperatives, rural consumer cooperatives, rural consumer cooperatives of water users, a map of their location in the context of regions of the country is shown, problems hindering their development are revealed, particularly the formation and development trends of each of them, the economic indicators of production of products are given, together with their organizational structure, etc. On the basis of the conducted analysis of the production conditions, rural consumers and rural consumer cooperatives of water users, problems hindering their development are revealed, the positive and negative trends in the development of various forms of agricultural cooperation are assessed, and proposals has been substantiated in order to improve the regulatory framework, mechanisms of state support, credit and financial mechanisms, etc.

  14. Impact of regulatory science on global public health

    OpenAIRE

    Patel, Meghal; Miller, Margaret Ann

    2012-01-01

    Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted followi...

  15. Collective-goal ascription increases cooperation in humans.

    Science.gov (United States)

    Mitkidis, Panagiotis; Sørensen, Jesper; Nielbo, Kristoffer L; Andersen, Marc; Lienard, Pierre

    2013-01-01

    Cooperation is necessary in many types of human joint activity and relations. Evidence suggests that cooperation has direct and indirect benefits for the cooperators. Given how beneficial cooperation is overall, it seems relevant to investigate the various ways of enhancing individuals' willingness to invest in cooperative endeavors. We studied whether ascription of a transparent collective goal in a joint action promotes cooperation in a group. A total of 48 participants were assigned in teams of 4 individuals to either a "transparent goal-ascription" or an "opaque goal-ascription" condition. After the manipulation, the participants played an anonymous public goods game with another member of their team. We measured the willingness of participants to cooperate and their expectations about the other player's contribution. Between subjects analyses showed that transparent goal ascription impacts participants' likelihood to cooperate with each other in the future, thereby greatly increasing the benefits from social interactions. Further analysis showed that this could be explained with a change in expectations about the partner's behavior and by an emotional alignment of the participants. The study found that a transparent goal ascription is associated with an increase of cooperation. We propose several high-level mechanisms that could explain the observed effect: general affect modulation, trust, expectation and perception of collective efficacy.

  16. Collective-goal ascription increases cooperation in humans.

    Directory of Open Access Journals (Sweden)

    Panagiotis Mitkidis

    Full Text Available BACKGROUND: Cooperation is necessary in many types of human joint activity and relations. Evidence suggests that cooperation has direct and indirect benefits for the cooperators. Given how beneficial cooperation is overall, it seems relevant to investigate the various ways of enhancing individuals' willingness to invest in cooperative endeavors. We studied whether ascription of a transparent collective goal in a joint action promotes cooperation in a group. METHODS: A total of 48 participants were assigned in teams of 4 individuals to either a "transparent goal-ascription" or an "opaque goal-ascription" condition. After the manipulation, the participants played an anonymous public goods game with another member of their team. We measured the willingness of participants to cooperate and their expectations about the other player's contribution. RESULTS: Between subjects analyses showed that transparent goal ascription impacts participants' likelihood to cooperate with each other in the future, thereby greatly increasing the benefits from social interactions. Further analysis showed that this could be explained with a change in expectations about the partner's behavior and by an emotional alignment of the participants. CONCLUSION: The study found that a transparent goal ascription is associated with an increase of cooperation. We propose several high-level mechanisms that could explain the observed effect: general affect modulation, trust, expectation and perception of collective efficacy.

  17. Spatial self-organization favors heterotypic cooperation over cheating

    Science.gov (United States)

    Momeni, Babak; Waite, Adam James; Shou, Wenying

    2013-01-01

    Heterotypic cooperation—two populations exchanging distinct benefits that are costly to produce—is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In ‘partner choice’, cooperators recognize and choose cooperating over cheating partners; in ‘partner fidelity feedback’, fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001 PMID:24220506

  18. Joint research to build a foundation for nuclear cooperation between Korea and China (KINS-NNSA)

    Energy Technology Data Exchange (ETDEWEB)

    Chung, J. K. [Korea Atomic Energy Research Institute, Taejeon (Korea); Park, D. K.; Eun, Y. S.; Lee, J. I.; Park, Y. S.; Song, I. J.; Bang, Y. S.; Hyun, C. H.; Jung, D. W.; Jung, J. W.; Lee, J. H.; Kang, S. C.; Lee, S. H.; Kim, H. Y.; Ryu, Y. H.; Bae, K H.; Ahn, S. H.; Jo, D. H. [Korea Institute of Nuclear Safety, Taejeon (Korea)

    2000-03-01

    In order to strengthen and effectively perform nuclear cooperation between Korea and China. This joint research is not only to develop cooperative programme but also to establish implementation direction for the cooperation between KINS and NNSA as nuclear regulatory bodies. Through this research; 1) Regulatory system, organization, function, and activities of Chinese regulatory bodies could be identified. 2) Both institutions agreed to follow cooperative programmes for nuclear safety, such as: - held annually regular meeting on technical informations and experts exchange - Immediate exchange the informations on NPP operational events each other and establishment of channel for this purpose - Immediate notification each other in the radiological nuclear accident and establishment of channel for this purpose - Cooperative safety research for mutual interests in the field of nuclear safety analysis technology 3) It is understood each other that both institutions will make into effort bilateral cooperation between Korea and China to advance triple cooperation among Korea, China and Japan. It is thought that this research makes nuclear safety cooperation between the two assist export of our predominant technology to China in the future. 7 refs., 5 tabs. (Author)

  19. Fundamental Limits of Cooperation

    CERN Document Server

    Lozano, Angel; Andrews, Jeffrey G

    2012-01-01

    Cooperation is viewed as a key ingredient for interference management in wireless systems. This paper shows that cooperation has fundamental limitations. The main result is that even full cooperation between transmitters cannot in general change an interference-limited network to a noise-limited network. The key idea is that there exists a spectral efficiency upper bound that is independent of the transmit power. First, a spectral efficiency upper bound is established for systems that rely on pilot-assisted channel estimation; in this framework, cooperation is shown to be possible only within clusters of limited size, which are subject to out-of-cluster interference whose power scales with that of the in-cluster signals. Second, an upper bound is also shown to exist when cooperation is through noncoherent communication; thus, the spectral efficiency limitation is not a by-product of the reliance on pilot-assisted channel estimation. Consequently, existing literature that routinely assumes the high-power spect...

  20. Communication Regulatory Science: Mapping a New Field.

    Science.gov (United States)

    Noar, Seth M; Cappella, Joseph N; Price, Simani

    2017-12-13

    Communication regulatory science is an emerging field that uses validated techniques, tools, and models to inform regulatory actions that promote optimal communication outcomes and benefit the public. In the opening article to this special issue on communication and tobacco regulatory science, we 1) describe Food and Drug Administration (FDA) regulation of tobacco products in the US; 2) introduce communication regulatory science and provide examples in the tobacco regulatory science realm; and 3) describe the special issue process and final set of articles. Communication research on tobacco regulatory science is a burgeoning area of inquiry, and this work advances communication science, informs and potentially guides the FDA, and may help to withstand legal challenges brought by the tobacco industry. This research has the potential to have a major impact on the tobacco epidemic and population health by helping implement the most effective communications to prevent tobacco initiation and increase cessation. This special issue provides an example of 10 studies that exemplify tobacco regulatory science and demonstrate how the health communication field can affect regulation and benefit public health.

  1. Regulatory analysis technical evaluation handbook. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-01

    The purpose of this Handbook is to provide guidance to the regulatory analyst to promote preparation of quality regulatory analysis documents and to implement the policies of the Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission (NUREG/BR-0058 Rev. 2). This Handbook expands upon policy concepts included in the NRC Guidelines and translates the six steps in preparing regulatory analyses into implementable methodologies for the analyst. It provides standardized methods of preparation and presentation of regulatory analyses, with the inclusion of input that will satisfy all backfit requirements and requirements of NRC`s Committee to Review Generic Requirements. Information on the objectives of the safety goal evaluation process and potential data sources for preparing a safety goal evaluation is also included. Consistent application of the methods provided here will result in more directly comparable analyses, thus aiding decision-makers in evaluating and comparing various regulatory actions. The handbook is being issued in loose-leaf format to facilitate revisions. NRC intends to periodically revise the handbook as new and improved guidance, data, and methods become available.

  2. Gene expression noise in spatial patterning: hunchback promoter structure affects noise amplitude and distribution in Drosophila segmentation.

    Directory of Open Access Journals (Sweden)

    David M Holloway

    2011-02-01

    Full Text Available Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb gene in early fruit fly (Drosophila segmentation by the maternally-derived gradient of the Bicoid (Bcd protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F, and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback, the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

  3. Evolution, epigenetics and cooperation.

    Science.gov (United States)

    Bateson, Patrick

    2014-04-01

    Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the organism and higher-order assemblages of organisms. These ideas impact on the theories of how cooperation might have evolved. Two of the theories, i.e. that cooperating individuals are genetically related or that they cooperate for self-interested reasons, have been accepted for a long time. The idea that adaptation takes place at the level of groups is much more controversial. However, bringing together studies of development with those of evolution is taking away much of the heat in the debate about the evolution of group behaviour.

  4. Cooperative Prototyping Experiments

    DEFF Research Database (Denmark)

    Bødker, Susanne; Grønbæk, Kaj

    1989-01-01

    This paper describes experiments with a design technique that we denote cooperative prototyping. The experiments consider design of a patient case record system for municipal dental clinics in which we used HyperCard, an off the shelf programming environment for the Macintosh. In the ecperiments we...... tried to achieve a fluent work-like evaluation of prototypes where users envisioned future work with a computer tool, at the same time as we made on-line modifications of prototypes in cooperation with the users when breakdown occur in their work-like evaluation. The experiments showed...... that it was possible to make a number of direct manipulation changes of prototypes in cooperation with the users, in interplay with their fluent work-like evaluation of these. However, breakdown occurred in the prototyping process when we reached the limits of the direct manipulation support for modification. From...

  5. Nordic Energy Policy Cooperation

    DEFF Research Database (Denmark)

    Jørgensen, Birte Holst

    2016-01-01

    by a committee of senior officials and a secretariat. This was characterised by an incremental development of the cooperation based on consensus, mutual understanding and trust facilitated through exchange of experiences, work groups, seminars, educational activities and mobility schemes for energy policy......, not least in the power sector. Over the years, five focus areas have been addressed. Energy security of supply triggered the Nordic cooperation with the need to develop a long-term energy policy. This required decision-making support and energy systems analyses based on reliable and valid data, modelling...... the borders long before the politicians supported and pushed for further cooperation. Energy efficiency was addressed by a portfolio of activities ranging from knowledge-sharing, public campaigns, labelling and standardisation of products. The need to address environmental degradation was inspired by the UN...

  6. Synchrony and cooperation.

    Science.gov (United States)

    Wiltermuth, Scott S; Heath, Chip

    2009-01-01

    Armies, churches, organizations, and communities often engage in activities-for example, marching, singing, and dancing-that lead group members to act in synchrony with each other. Anthropologists and sociologists have speculated that rituals involving synchronous activity may produce positive emotions that weaken the psychological boundaries between the self and the group. This article explores whether synchronous activity may serve as a partial solution to the free-rider problem facing groups that need to motivate their members to contribute toward the collective good. Across three experiments, people acting in synchrony with others cooperated more in subsequent group economic exercises, even in situations requiring personal sacrifice. Our results also showed that positive emotions need not be generated for synchrony to foster cooperation. In total, the results suggest that acting in synchrony with others can increase cooperation by strengthening social attachment among group members.

  7. Cooperation between referees and authors increases peer review accuracy.

    Science.gov (United States)

    Leek, Jeffrey T; Taub, Margaret A; Pineda, Fernando J

    2011-01-01

    Peer review is fundamentally a cooperative process between scientists in a community who agree to review each other's work in an unbiased fashion. Peer review is the foundation for decisions concerning publication in journals, awarding of grants, and academic promotion. Here we perform a laboratory study of open and closed peer review based on an online game. We show that when reviewer behavior was made public under open review, reviewers were rewarded for refereeing and formed significantly more cooperative interactions (13% increase in cooperation, P = 0.018). We also show that referees and authors who participated in cooperative interactions had an 11% higher reviewing accuracy rate (P = 0.016). Our results suggest that increasing cooperation in the peer review process can lead to a decreased risk of reviewing errors.

  8. Cooperation between referees and authors increases peer review accuracy.

    Directory of Open Access Journals (Sweden)

    Jeffrey T Leek

    Full Text Available Peer review is fundamentally a cooperative process between scientists in a community who agree to review each other's work in an unbiased fashion. Peer review is the foundation for decisions concerning publication in journals, awarding of grants, and academic promotion. Here we perform a laboratory study of open and closed peer review based on an online game. We show that when reviewer behavior was made public under open review, reviewers were rewarded for refereeing and formed significantly more cooperative interactions (13% increase in cooperation, P = 0.018. We also show that referees and authors who participated in cooperative interactions had an 11% higher reviewing accuracy rate (P = 0.016. Our results suggest that increasing cooperation in the peer review process can lead to a decreased risk of reviewing errors.

  9. Excited cooper pairs

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Arrietea, M. G.; Solis, M. A.; De Llano, M. [Universidad Nacional Autonoma de Mexico, Mexico, D.F (Mexico)

    2001-02-01

    Excited cooper pairs formed in a many-fermion system are those with nonzero total center-of mass momentum (CMM). They are normally neglected in the standard Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity for being too few compared with zero CMM pairs. However, a Bose-Einstein condensation picture requires both zero and nonzero CMM pairs. Assuming a BCS model interaction between fermions we determine the populations for all CMM values of Cooper pairs by actually calculating the number of nonzero-CMM pairs relative to that of zero-CMM ones in both 2D and 3D. Although this ratio decreases rapidly with CMM, the number of Cooper pairs for any specific CMM less than the maximum (or breakup of the pair) momentum turns out to be typically larger than about 95% of those with zero-CMM at zero temperature T. Even at T {approx}100 K this fraction en 2D is still as large as about 70% for typical quasi-2D cuprate superconductor parameters. [Spanish] Los pares de cooper excitados formados en un sistema de muchos electrones, son aquellos con momentos de centro de masa (CMM) diferente de cero. Normalmente estos no son tomados en cuenta en la teoria estandar de la superconductividad de Bardeen-Cooper-Schrieffer (BCS) al suponer que su numero es muy pequeno comparados con los pares de centro de masa igual a cero. Sin embargo, un esquema de condensacion Bose-Einstein requiere de ambos pares, con CMM cero y diferente de cero. Asumiendo una interaccion modelo BCS entre los fermiones, determinamos la poblacion de pares cooper con cada uno de todos los posibles valores del CMM calculando el numero de pares con momentos de centro de masa diferente de cero relativo a los pares de CMM igual a cero, en 2D y 3D. Aunque esta razon decrece rapidamente con el CMM, el numero de pares de cooper para cualquier CMM especifico menor que el momento maximo (o rompimiento de par) es tipicamente mas grande que el 95% de aquellos con CMM cero. Aun a T {approx}100 K esta fraccion en 2D es

  10. Cooperative strategies in innovation

    Directory of Open Access Journals (Sweden)

    Ratner Svetlana Valerevna

    2013-12-01

    Full Text Available In the knowledge economy one of the conventional ways to obtain economic agents access to new knowledge and technology is the creation and implementation of specific cooperative strategies, such as the formation of alliances with other economic agents. Combining competencies partners in joint research and development has a positive impact on innovation, but it is a partial convergence of competences partners that in the long term can lead to the unification of competences agents economic system and reduce their innovative activity. In this paper, we propose an effective method of information management in the implementation of a cooperative strategy of innovation.

  11. Membership in cooperative societies

    Directory of Open Access Journals (Sweden)

    Eba Gaminde Egia

    2017-12-01

    Full Text Available In this work we will analyze the practical application of one of the cooperative principles, «voluntary and free membership», referring to the entering of members in cooperative societies. We will first explain the meaning of this principle, and then bring up its normative regulation, with special emphasis on those aspects in which our autonomic laws differ, and ending with a brief reference to the economic aspect and the different ways to make contributions and their consequences.Received: 31 May 2017Accepted: 14 October 2017Published online: 22 December 2017

  12. Introduction: cooperative learning

    Directory of Open Access Journals (Sweden)

    José-Manuel Serrano

    2014-10-01

    Full Text Available The principal objective of this revision is the recognition of cooperative learning as a highly effective strategy for the accomplishment of the general goals in learning. The different investigations assessed validate the potential that a cooperative organization of the classroom could entail for academic achievement, self-esteem, interpersonal attraction or social support. The solidity of the existing research contributes to its external and internal validity and, thus, to conclude that the results are consistent and can be extrapolated to different cultures, ethnic groups or countries.

  13. Developments in cooperative learning: review of research

    Directory of Open Access Journals (Sweden)

    Robyn M. Gillies

    2014-10-01

    Full Text Available Cooperative learning, where students work in small groups to accomplish shared goals, is widely recognized as a teaching strategy that promotes learning and socialization among students from kindergarten through college and across different subject domains. It has been used successfully to promote reading and writing achievements, understanding and conceptual development in science classes, problem-solving in mathematics, and higher-order thinking and learning to name just a few. It has been shown to enhance students' willingness to work cooperatively and productively with others with diverse learning and adjustment needs and to enhance intergroup relations with those from culturally and ethnically different backgrounds. It has also been used as a teaching strategy to assist students to manage conflict and to help students identified as bullies learn appropriate interpersonal skills. In fact, it has been argued that cooperative learning experiences are crucial to preventing and alleviating many of the social problems related to children, adolescents, and young adults. There is no doubt that the benefits attributed to cooperative learning are widespread and numerous and it is the apparent success of this approach to learning that has led to it being acclaimed as one of the greatest educational innovations of recent times. The purpose of this paper is not only to review developments in research on cooperative learning but also to examine the factors that mediate and moderate its success. In particular, the review focuses on the types of student and teacher interactions generated and the key role talk plays in developing student thinking and learning, albeit through the expression of contrasting opinions or constructed shared meaning. The intention is to provide additional insights on how teachers can effectively utilize this pedagogical approach to teaching and learning in their classrooms.

  14. Cooperatives for “fair globalization”? Indigenous people, cooperatives, and corporate social responsibility in the Brazilian Amazon.

    Science.gov (United States)

    Burke, Brian J

    2010-01-01

    Cooperatives and socially responsible corporations are being hailed as possible correctives to the socioeconomic and ecological exploitation of transnational capitalism. AmazonCoop—a cooperative linking indigenous Brazil nut harvesters and the multinational firm The Body Shop through trade and development projects—capitalized on indigenous symbolism to generate significant material benefits for both parties. At the same time, however, it made indigenous people more vulnerable and dependent, failed to promote participatory development, masked the effects of unfavorable state policies, and perpetuated discriminatory distinctions among indigenous people. Furthermore, the cooperative did not provide an organizational framework to ameliorate the vulnerabilities of indigenous identity politics or transform symbolic capital into enduring political-economic change. This case strongly supports arguments that cooperatives must be rooted in participation, democratic member control, and autonomy if they are to promote “fair globalization” or social transformation rather than institutionalize existing patterns of exploitation.

  15. Cooperatives between truth and validity

    Directory of Open Access Journals (Sweden)

    Guilherme Krueger

    2014-12-01

    Full Text Available The current declaration of the International Cooperative Alliance on cooperative identity since its 1995 Centennial Conference (which was held in Manchester makes no distinction between cooperation and cooperative. The lack of distinction between cooperation and cooperative has caused the Decennial Cooperative Action Plan to define cooperatives as a form, while their materiality is regarded as managerial: a business (activity under a cooperative form. An identity that is close to us cannot be reduced to form, without this being a problem. Therefore, the value underlying this identity —cooperation— must have a substantial basis, even if it is idealised, if it is to affect us.Received: 27.03.2014Accepted: 12.05.2014

  16. The self-antigen, thyroglobulin, induces antigen-experienced CD4+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Galdiers, Marcel P; Hedegaard, Chris J

    2010-01-01

    . Whereas TT induced pro-inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL-5], TG evoked persistent release of the regulatory IL-10. Some donors, however, also responded with late IFN-gamma production, suggesting that the regulation by IL-10 could be overridden. Although...... peripheral tolerance towards TG in the normal population, with aberrant balance between pro- and anti-inflammatory cytokine responses for some donors. This observation has implications for autoantigen recognition in general, and provides a basis for investigating the dichotomy between physiological...

  17. H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells.

    OpenAIRE

    Karmodiya Krishanpal; Krebs Arnaud R; Oulad-Abdelghani Mustapha; Kimura Hiroshi; Tora Laszlo

    2012-01-01

    Abstract Background Transcription regulation in pluripotent embryonic stem (ES) cells is a complex process that involves multitude of regulatory layers, one of which is post-translational modification of histones. Acetylation of specific lysine residues of histones plays a key role in regulating gene expression. Results Here we have investigated the genome-wide occurrence of two histone marks, acetylation of histone H3K9 and K14 (H3K9ac and H3K14ac), in mouse embryonic stem (mES) cells. Genom...

  18. The self-antigen, thyroglobulin, induces antigen-experienced CD4+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes

    DEFF Research Database (Denmark)

    Nielsen, Claus Kim Hostein; Galdiers, Marcel P; Hedegaard, Chris Juul

    2010-01-01

    . Whereas TT induced pro-inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL-5], TG evoked persistent release of the regulatory IL-10. Some donors, however, also responded with late IFN-gamma production, suggesting that the regulation by IL-10 could be overridden. Although...... monocytes were prime producers of IL-10 in the early TG response, a few IL-10-secreting CD4(+) T cells, primarily with CD45RO(+) memory phenotype, were also detected. Furthermore, T-cell depletion from the mononuclear cell preparation abrogated monocyte IL-10 production. Our findings indicate active...

  19. The evolution of cooperation by negotiation in a noisy world.

    Science.gov (United States)

    Ito, K; McNamara, J M; Yamauchi, A; Higginson, A D

    2017-03-01

    Cooperative interactions among individuals are ubiquitous despite the possibility of exploitation by selfish free riders. One mechanism that may promote cooperation is 'negotiation': individuals altering their behaviour in response to the behaviour of others. Negotiating individuals decide their actions through a recursive process of reciprocal observation, thereby reducing the possibility of free riding. Evolutionary games with response rules have shown that infinitely many forms of the rule can be evolutionarily stable simultaneously, unless there is variation in individual quality. This potentially restricts the conditions under which negotiation could maintain cooperation. Organisms interact with one another in a noisy world in which cooperative effort and the assessment of effort may be subject to error. Here, we show that such noise can make the number of evolutionarily stable rules finite, even without quality variation, and so noise could help maintain cooperative behaviour. We show that the curvature of the benefit function is the key factor determining whether individuals invest more or less as their partner's investment increases, investing less when the benefit to investment has diminishing returns. If the benefits of low investment are very small then behavioural flexibility tends to promote cooperation, because negotiation enables cooperators to reach large benefits. Under some conditions, this leads to a repeating cycle in which cooperative behaviour rises and falls over time, which may explain between-population differences in cooperative behaviour. In other conditions, negotiation leads to extremely high levels of cooperative behaviour, suggesting that behavioural flexibility could facilitate the evolution of eusociality in the absence of high relatedness. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  20. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

    DEFF Research Database (Denmark)

    Martinat, Cecile; Bacci, Jean-Jacques; Leete, Thomas

    2006-01-01

    Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson......'s disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1......, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation...

  1. Research cooperation promoting project in fiscal 1998. Research cooperation related to developing mine resources extraction and treatment technologies of environment harmonizing and high efficiency type; 1998 nendo kenkyu kyoryoku suishin jigyo. Kankyo chowagata kokoritsu kobutsu shigen chushutsu shori gijutsu no kaihatsu ni kansuru kenkyu kyoryoku

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    In order to realize more effective utilization of non-ferrous metal resources, joint research cooperation is made with the Republic of Kazakhstan. It is intended that valuable metals (gold, silver, copper, rare metals, and others) contained at large quantity in ore scraps generated in association with mine operation be extracted and recovered efficiently paying considerations to the environment. The treatment process consists of the following conception: raw materials such as ore scraps are leached by sulfuric acid and microorganisms to separate and recover gold and silver; the leach liquor containing valuable metals is extracted by using solvent and recovered of copper and rare metals via an electrolytic process; and the waste water is treated and discharged. Fiscal 1998 has performed studies on the wet treatment system at the site and in Japan, the gold and silver treatment, and the waste water treatment by using samples collected from the site in fiscal 1996. Based on the results of these fundamental studies, a pilot plant was built, and all of the facility fabrication was completed in fiscal 1998. Part of the facilities has been transported to the site. To drive the project forward effectively, materials and items of equipment required for the joint research were procured and transported to the country, and at the same time Kazakhstanian researchers were received in Japan for training. (NEDO)

  2. Development cooperation as methodology for teaching social responsibility to engineers

    Science.gov (United States)

    Lappalainen, Pia

    2011-12-01

    The role of engineering in promoting global well-being has become accentuated, turning the engineering curriculum into a means of dividing well-being equally. The gradual fortifying calls for humanitarian engineering have resulted in the incorporation of social responsibility themes in the university curriculum. Cooperation, communication, teamwork, intercultural cooperation, sustainability, social and global responsibility represent the socio-cultural dimensions that are becoming increasingly important as globalisation intensifies the demands for socially and globally adept engineering communities. This article describes an experiment, the Development Cooperation Project, which was conducted at Aalto University in Finland to integrate social responsibility themes into higher engineering education.

  3. The influence of migration speed on cooperation in spatial games

    Science.gov (United States)

    Li, Wen-Jing; Jiang, Luo-Luo; Gu, Changgui; Yang, Huijie

    2017-12-01

    Migration is a common phenomenon in human society which provides a person an opportunity to search for a new life from one area to another. In the framework of game theory, people may migrate to escape from a current adverse environment (evading defection). Since people may migrate at different speeds, it is interesting to figure out the influence of migration speed on the evolution of cooperative behavior. In an attempt to discover the influence, we propose here a model based on an adaptive migration mechanism. In this model, an individual migrates or updates his/her strategy asynchronously, which is tuned by migration frequency. Firstly, it is found that an appropriate migration speed may evoke an effective mechanism, which enables cooperators dominate even in highly adverse conditions. Secondly, we check how migration speed alters the paradigm of cooperation quantitatively in the conditions of different migration frequency. When migration frequency is high, cooperation is promoted only at a small migration speed. However, when migration frequency is low, cooperation is always promoted at any migration speed. In addition, we also investigated the influence of temptation to defect on cooperation for the case of different migration speeds and migration frequencies. Our results may provide a fresh perspective on the understanding of how human behavior affects cooperation.

  4. Cooperative Learning and Teaching

    Science.gov (United States)

    Jacobs, G. M.; Kimura, H.

    2013-01-01

    In and out of the classroom, life would be unthinkable without interacting with fellow humans. This book urges more cooperative and group activities in the English language classroom for all the advantages: students use the target language more, help each other with comprehension, receive attention from peers as well as the teacher, are motivated…

  5. Does intuition cause cooperation?

    NARCIS (Netherlands)

    P.P.J.L. Verkoeijen (Peter); S. Bouwmeester (Samantha)

    2014-01-01

    textabstractRecently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more

  6. Cooperative Mobile Sensing Networks

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R S; Kent, C A; Jones, E D; Cunningham, C T; Armstrong, G W

    2003-02-10

    A cooperative control architecture is presented that allows a fleet of Unmanned Air Vehicles (UAVs) to collect data in a parallel, coordinated and optimal manner. The architecture is designed to react to a set of unpredictable events thereby allowing data collection to continue in an optimal manner.

  7. Physicality and Cooperative Design

    NARCIS (Netherlands)

    Vyas, Dhaval; Heylen, Dirk K.J.; Nijholt, Antinus; Popescu-Belis, Andrei; Stiefelhagen, Rainer

    2008-01-01

    CSCW researchers have increasingly come to realize that material work setting and its population of artefacts play a crucial part in coordination of distributed or co-located work. This paper uses the notion of physicality as a basis to understand cooperative work. Using examples from an ongoing

  8. Cooper's Hawk (Accipiter cooperii)

    Science.gov (United States)

    Jean-Luc E. Cartron; Patricia L. Kennedy; Rob Yaksich; Scott H. Stoleson

    2010-01-01

    The Cooper's Hawk (Accipiter cooperii) is intermediate in size between the Northern Goshawk (Accipiter gentilis) and the Sharp-shinned Hawk (A. striatus), northern North America's other two accipiters. The two sexes are almost alike in plumage, but as in both of the other species, the female is noticeably larger. According to Wheeler and Clark (1995), a...

  9. Designs for Cooperative Interactions.

    Science.gov (United States)

    Fogarty, Robin

    Educators are moving toward models of instruction that contain a myriad of interaction patterns among teachers and students. This shift from didactic teaching models to intensely involving designs is difficult for teachers, but is made easier if seen as a gradual change. This book provides an overview of 12 cooperative interaction designs for the…

  10. Cooperative Alaska Forest Inventory

    Science.gov (United States)

    Thomas Malone; Jingjing Liang; Edmond C. Packee

    2009-01-01

    The Cooperative Alaska Forest Inventory (CAFI) is a comprehensive database of boreal forest conditions and dynamics in Alaska. The CAFI consists of field-gathered information from numerous permanent sample plots distributed across interior and south-central Alaska including the Kenai Peninsula. The CAFI currently has 570 permanent sample plots on 190 sites...

  11. Indian Ocean Rim Cooperation

    DEFF Research Database (Denmark)

    Wippel, Steffen

    Since the mid-1990s, the Indian Ocean has been experiencing increasing economic cooperation among its rim states. Middle Eastern countries, too, participate in the work of the Indian Ocean Rim Association, which received new impetus in the course of the current decade. Notably Oman is a very active...

  12. Communication, Coordination, Cooperation.

    Science.gov (United States)

    Rose, Nancy Oft; Wiper, Kathie Tippens

    Speech communication teachers at both secondary and postsecondary school levels must cooperate to improve oral communication education. Despite the importance of oral communication skills, speech courses are rarely required in high school. Teachers must tell school boards, higher education boards, and faculties of the importance of speaking and…

  13. Why do people cooperate with medical research? Findings from three studies.

    Science.gov (United States)

    Dixon-Woods, Mary; Tarrant, Carolyn

    2009-06-01

    In this paper, we distinguish decisions about cooperation with medical research from decisions about research participation. We offer an empirical and theoretical exploration of why people in three different UK-based medical research projects chose to cooperate. Data analysis of the accounts of 128 participants across the three studies was based on the constant comparative method. Participants' cooperation was engaged by a perception that they would be contributing to the 'public good', but they also wanted to justify their decision as sensible and safe. Critical to their cooperation was their belief that researchers would fulfil their side of the cooperative bargain, by not exposing participants to risks of harm or exploitation. Although participants were generally unaware of the details of the regulatory regime for research, they demonstrated a generalised reliance on regulation as a feature of everyday life that would provide a safe context for cooperation. In their assessment of particular projects, participants made judgements about whether to cooperate based on more specific cues, which acted as signs to assure them that researchers shared their cooperative intentions. These cues included organisational and professional credentials, the role identities and perceived trustworthiness of those involved in recruiting to research, and visible signs of reasonable practice mandated by regulatory systems. Thus participants drew on their understandings of an institutional field that was much broader than that of research alone. We propose that the social organisation of research is fundamental to the judgements people make about cooperation with research. Cooperation may be a more useful way of thinking about how people come to engage in collaboratively oriented actions such as research participation, rather than currently dominant individualistic models. Attention to the institutional context of research is critical to understanding what makes cooperation possible

  14. Regulatory Information By Sector

    Science.gov (United States)

    Find environmental regulatory, compliance, & enforcement information for various business, industry and government sectors, listed by NAICS code. Sectors include agriculture, automotive, petroleum manufacturing, oil & gas extraction & other manufacturing

  15. Functional characterization of variations on regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Michal Lapidot

    2008-03-01

    Full Text Available Transcription factors (TFs regulate gene expression through specific interactions with short promoter elements. The same regulatory protein may recognize a variety of related sequences. Moreover, once they are detected it is hard to predict whether highly similar sequence motifs will be recognized by the same TF and regulate similar gene expression patterns, or serve as binding sites for distinct regulatory factors. We developed computational measures to assess the functional implications of variations on regulatory motifs and to compare the functions of related sites. We have developed computational means for estimating the functional outcome of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. We predict the effects of nucleotide variations within motifs on gene expression patterns. In cases where such predictions could be compared to suitable published experimental evidence, we found very good agreement. We further accumulated statistics from multiple substitutions across various binding sites in an attempt to deduce general properties that characterize nucleotide substitutions that are more likely to alter expression. We found that substitutions involving Adenine are more likely to retain the expression pattern and that substitutions involving Guanine are more likely to alter expression compared to the rest of the substitutions. Our results should facilitate the prediction of the expression outcomes of binding site variations. One typical important implication is expected to be the ability to predict the phenotypic effect of variation in regulatory motifs in promoters.

  16. 76 FR 69719 - Gregory R. Swecker and Beverly F. Swecker v. Midland Power Cooperative and State of Iowa; Notice...

    Science.gov (United States)

    2011-11-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Gregory R. Swecker and Beverly F. Swecker v. Midland Power Cooperative and... by Midland Power Cooperative (Respondent) and request for an expedited order for reconnection. In...

  17. 76 FR 28019 - Gregory R. Swecker, Beverly F. Swecker v. Midland Power Cooperative, State of Iowa; Notice of...

    Science.gov (United States)

    2011-05-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Gregory R. Swecker, Beverly F. Swecker v. Midland Power Cooperative, State... the requirements of PURPA against Midland Power Cooperative and the State of Iowa (Respondents...

  18. Evolution of cooperation driven by social-welfare-based migration

    Science.gov (United States)

    Li, Yan; Ye, Hang; Zhang, Hong

    2016-03-01

    Individuals' migration behavior may play a significant role in the evolution of cooperation. In reality, individuals' migration behavior may depend on their perceptions of social welfare. To study the relationship between social-welfare-based migration and the evolution of cooperation, we consider an evolutionary prisoner's dilemma game (PDG) in which an individual's migration depends on social welfare but not on the individual's own payoff. By introducing three important social welfare functions (SWFs) that are commonly studied in social science, we find that social-welfare-based migration can promote cooperation under a wide range of parameter values. In addition, these three SWFs have different effects on cooperation, especially through the different spatial patterns formed by migration. Because the relative efficiency of the three SWFs will change if the parameter values are changed, we cannot determine which SWF is optimal for supporting cooperation. We also show that memory capacity, which is needed to evaluate individual welfare, may affect cooperation levels in opposite directions under different SWFs. Our work should be helpful for understanding the evolution of human cooperation and bridging the chasm between studies of social preferences and studies of social cooperation.

  19. Reinforcement Learning Explains Conditional Cooperation and Its Moody Cousin.

    Science.gov (United States)

    Ezaki, Takahiro; Horita, Yutaka; Takezawa, Masanori; Masuda, Naoki

    2016-07-01

    Direct reciprocity, or repeated interaction, is a main mechanism to sustain cooperation under social dilemmas involving two individuals. For larger groups and networks, which are probably more relevant to understanding and engineering our society, experiments employing repeated multiplayer social dilemma games have suggested that humans often show conditional cooperation behavior and its moody variant. Mechanisms underlying these behaviors largely remain unclear. Here we provide a proximate account for this behavior by showing that individuals adopting a type of reinforcement learning, called aspiration learning, phenomenologically behave as conditional cooperator. By definition, individuals are satisfied if and only if the obtained payoff is larger than a fixed aspiration level. They reinforce actions that have resulted in satisfactory outcomes and anti-reinforce those yielding unsatisfactory outcomes. The results obtained in the present study are general in that they explain extant experimental results obtained for both so-called moody and non-moody conditional cooperation, prisoner's dilemma and public goods games, and well-mixed groups and networks. Different from the previous theory, individuals are assumed to have no access to information about what other individuals are doing such that they cannot explicitly use conditional cooperation rules. In this sense, myopic aspiration learning in which the unconditional propensity of cooperation is modulated in every discrete time step explains conditional behavior of humans. Aspiration learners showing (moody) conditional cooperation obeyed a noisy GRIM-like strategy. This is different from the Pavlov, a reinforcement learning strategy promoting mutual cooperation in two-player situations.

  20. Reinforcement Learning Explains Conditional Cooperation and Its Moody Cousin.

    Directory of Open Access Journals (Sweden)

    Takahiro Ezaki

    2016-07-01

    Full Text Available Direct reciprocity, or repeated interaction, is a main mechanism to sustain cooperation under social dilemmas involving two individuals. For larger groups and networks, which are probably more relevant to understanding and engineering our society, experiments employing repeated multiplayer social dilemma games have suggested that humans often show conditional cooperation behavior and its moody variant. Mechanisms underlying these behaviors largely remain unclear. Here we provide a proximate account for this behavior by showing that individuals adopting a type of reinforcement learning, called aspiration learning, phenomenologically behave as conditional cooperator. By definition, individuals are satisfied if and only if the obtained payoff is larger than a fixed aspiration level. They reinforce actions that have resulted in satisfactory outcomes and anti-reinforce those yielding unsatisfactory outcomes. The results obtained in the present study are general in that they explain extant experimental results obtained for both so-called moody and non-moody conditional cooperation, prisoner's dilemma and public goods games, and well-mixed groups and networks. Different from the previous theory, individuals are assumed to have no access to information about what other individuals are doing such that they cannot explicitly use conditional cooperation rules. In this sense, myopic aspiration learning in which the unconditional propensity of cooperation is modulated in every discrete time step explains conditional behavior of humans. Aspiration learners showing (moody conditional cooperation obeyed a noisy GRIM-like strategy. This is different from the Pavlov, a reinforcement learning strategy promoting mutual cooperation in two-player situations.

  1. Randomness in the evolution of cooperation.

    Science.gov (United States)

    Hadzibeganovic, Tarik; Stauffer, Dietrich; Han, Xiao-Pu

    2015-04-01

    Tag-based ethnocentric cooperation is a highly robust behavior which can evolve and prevail under a wide variety of conditions. Recent studies have demonstrated, however, that ethnocentrism can temporarily be suppressed by other competing strategies, especially in its early evolutionary stages. In a series of computational experiments, conducted with an agent-based evolutionary model of tag-mediated cooperation, we addressed the question of whether a stochastically established and once dominant non-ethnocentric strategy such as indiscriminate altruism can stably persist and permanently outweigh ethnocentrism. Our model, simulated on various complex network topologies, employs simple haploid genetics and asexual reproduction of computational agents equipped with memory and heritable phenotypic traits. We find that in combination with an implemented memory mechanism and tags, random bias acting in favor of altruists can lead to their long-lasting victory over all other types of strategists. The difference in density between altruistic and ethnocentric cooperators increases with greater rewiring of the underlying network, but decreases with growing population size. These findings suggest that randomness plays an important role in promoting non-ethnocentric cooperation and contributes to our understanding of how other than adaptive mechanisms can initiate the design of novel behavioral phenotypes, thereby shaping surprisingly new evolutionary pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A Cooperation Model Applied in a Kindergarten

    Directory of Open Access Journals (Sweden)

    Jose I. Rodriguez

    2011-10-01

    Full Text Available The need for collaboration in a global world has become a key factor for success for many organizations and individuals. However in several regions and organizations in the world, it has not happened yet. One of the settings where major obstacles occur for collaboration is in the business arena, mainly because of competitive beliefs that cooperation could hurt profitability. We have found such behavior in a wide variety of countries, in advanced and developing economies. Such cultural behaviors or traits characterized entrepreneurs by working in isolation, avoiding the possibilities of building clusters to promote regional development. The needs to improve the essential abilities that conforms cooperation are evident. It is also very difficult to change such conduct with adults. So we decided to work with children to prepare future generations to live in a cooperative world, so badly hit by greed and individualism nowadays. We have validated that working with children at an early age improves such behavior. This paper develops a model to enhance the essential abilities in order to improve cooperation. The model has been validated by applying it at a kindergarten school.

  3. Evolutionary Games of Multiplayer Cooperation on Graphs.

    Directory of Open Access Journals (Sweden)

    Jorge Peña

    2016-08-01

    Full Text Available There has been much interest in studying evolutionary games in structured populations, often modeled as graphs. However, most analytical results so far have only been obtained for two-player or linear games, while the study of more complex multiplayer games has been usually tackled by computer simulations. Here we investigate evolutionary multiplayer games on graphs updated with a Moran death-Birth process. For cycles, we obtain an exact analytical condition for cooperation to be favored by natural selection, given in terms of the payoffs of the game and a set of structure coefficients. For regular graphs of degree three and larger, we estimate this condition using a combination of pair approximation and diffusion approximation. For a large class of cooperation games, our approximations suggest that graph-structured populations are stronger promoters of cooperation than populations lacking spatial structure. Computer simulations validate our analytical approximations for random regular graphs and cycles, but show systematic differences for graphs with many loops such as lattices. In particular, our simulation results show that these kinds of graphs can even lead to more stringent conditions for the evolution of cooperation than well-mixed populations. Overall, we provide evidence suggesting that the complexity arising from many-player interactions and spatial structure can be captured by pair approximation in the case of random graphs, but that it need to be handled with care for graphs with high clustering.

  4. Evolutionary Games of Multiplayer Cooperation on Graphs.

    Science.gov (United States)

    Peña, Jorge; Wu, Bin; Arranz, Jordi; Traulsen, Arne

    2016-08-01

    There has been much interest in studying evolutionary games in structured populations, often modeled as graphs. However, most analytical results so far have only been obtained for two-player or linear games, while the study of more complex multiplayer games has been usually tackled by computer simulations. Here we investigate evolutionary multiplayer games on graphs updated with a Moran death-Birth process. For cycles, we obtain an exact analytical condition for cooperation to be favored by natural selection, given in terms of the payoffs of the game and a set of structure coefficients. For regular graphs of degree three and larger, we estimate this condition using a combination of pair approximation and diffusion approximation. For a large class of cooperation games, our approximations suggest that graph-structured populations are stronger promoters of cooperation than populations lacking spatial structure. Computer simulations validate our analytical approximations for random regular graphs and cycles, but show systematic differences for graphs with many loops such as lattices. In particular, our simulation results show that these kinds of graphs can even lead to more stringent conditions for the evolution of cooperation than well-mixed populations. Overall, we provide evidence suggesting that the complexity arising from many-player interactions and spatial structure can be captured by pair approximation in the case of random graphs, but that it need to be handled with care for graphs with high clustering.

  5. Cooperation and cheating in microbes

    Science.gov (United States)

    Gore, Jeff

    2011-03-01

    Understanding the cooperative and competitive dynamics within and between species is a central challenge in evolutionary biology. Microbial model systems represent a unique opportunity to experimentally test fundamental theories regarding the evolution of cooperative behaviors. In this talk I will describe our experiments probing cooperation in microbes. In particular, I will compare the cooperative growth of yeast in sucrose and the cooperative inactivation of antibiotics by bacteria. In both cases we find that cheater strains---which don't contribute to the public welfare---are able to take advantage of the cooperator strains. However, this ability of cheaters to out-compete cooperators occurs only when cheaters are present at low frequency, thus leading to steady-state coexistence. These microbial experiments provide fresh insight into the evolutionary origin of cooperation.

  6. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.

    Science.gov (United States)

    Almon, Einat; Khoury, Tawfik; Drori, Ariel; Gingis-Velitski, Svetlana; Alon, Sari; Chertkoff, Raul; Mushkat, Mordechai; Shaaltiel, Yoseph; Ilan, Yaron

    2017-07-01

    An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels. An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed. An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Organizational Fluidity and Sustainable Cooperation

    CERN Document Server

    Glance, N S; Glance, Natalie; Huberman, Bernardo

    1993-01-01

    Abstract We show that fluid organizations display higher levels of cooperation than attainable by groups with either a fixed social structure or lacking one altogether. By moving within the organization, individuals cause restructurings that facilitate cooperation. Computer experiments simulating fluid organizations faced with a social dilemma reveal a myriad of complex cooperative behaviors that result from the interplay between individual strategies and structural changes. Significantly, fluid organizations can display long cycles of sustained cooperation interrupted by short bursts of defection.

  8. Chromatin insulators: regulatory mechanisms and epigenetic inheritance

    Science.gov (United States)

    Bushey, Ashley M.; Dorman, Elizabeth R.; Corces, Victor G.

    2008-01-01

    Enhancer-blocking insulators are DNA elements that disrupt the communication between a regulatory sequence, such as an enhancer or a silencer, and a promoter. Insulators participate in both transcriptional regulation and global nuclear organization, two features of chromatin that are thought to be maintained from one generation to the next through epigenetic mechanisms. Furthermore, there are many regulatory mechanisms in place that enhance or hinder insulator activity. These modes of regulation could be used to establish cell-type specific insulator activity that is epigenetically inherited along a cell and/or organismal lineage. This review will discuss the evidence for epigenetic inheritance and regulation of insulator function. PMID:18851828

  9. Forestry cooperatives: past and present

    Science.gov (United States)

    Mark G. Rickenbach

    2006-01-01

    Forest landowner cooperatives are not a new phenomenon, but past efforts to create and sustain these businesses have been largely unsuccessful in the U.S. Before and just after World War II saw significant investment in cooperative development that failed to create durable business. The purpose of this chapter is to briefly describe the history of forestry cooperatives...

  10. Cooperative Learning in Elementary Schools

    Science.gov (United States)

    Slavin, Robert E.

    2015-01-01

    Cooperative learning refers to instructional methods in which students work in small groups to help each other learn. Although cooperative learning methods are used for different age groups, they are particularly popular in elementary (primary) schools. This article discusses methods and theoretical perspectives on cooperative learning for the…

  11. The governance of cooperative societies

    Directory of Open Access Journals (Sweden)

    Yaiza Juanes Sobradillo

    2005-12-01

    Full Text Available The present work aims to expose the appropriate legislation for cooperative societies to which Article 129 of the Spanish Constitution refers, deepen the analysis of the organs of management and control based on the Spanish and Basque Laws on Cooperatives and the Statute for the European Cooperative Societies.

  12. Cooperation preferences and framing effects

    NARCIS (Netherlands)

    Petit Dit Dariel, A.C.

    2013-01-01

    This paper presents the results from an experiment investigating whether framing affects the elicitation and predictive power of preferences for cooperation, i.e., the willingness to cooperate with others. Cooperation preferences are elicited in three treatments using the method of Fischbacher,

  13. Cooperative competition for future mobility

    NARCIS (Netherlands)

    Nunen, E. van; Kwakkernaat, M.R.J.A.E.; Ploeg, J.; Netten, B.D.

    2012-01-01

    In May 2011, the Grand Cooperative Driving Challenge (GCDC) was held, providing the possibility for teams to develop and compare their cooperative driving solutions in a competitive setting. The challenge was organized to further accelerate developments in the area of cooperative driving. Nine

  14. Cooperative Learning in Physical Education

    Science.gov (United States)

    Hannon, James C.; Ratliffe, Thomas

    2004-01-01

    A methodology that has not received as much attention in the physical education setting as in other subject areas is cooperative learning. Cooperative learning has been used for many years in math, science, and history, but not until recently has the concept been applied to physical education. Research conducted on cooperative learning has shown…

  15. Enlightening Advantages of Cooperative Learning

    Science.gov (United States)

    Faryadi, Qais

    2007-01-01

    This appraisal discusses the notion that cooperative learning enhances learners' emotional and social performance. It also observes the perception that cooperative learning dramatically improves students' academic accomplishment. This review also examines the definition of cooperative learning and attempts to define it through the lens of renowned…

  16. Junctionless Cooper pair transistor

    Energy Technology Data Exchange (ETDEWEB)

    Arutyunov, K. Yu., E-mail: konstantin.yu.arutyunov@jyu.fi [National Research University Higher School of Economics , Moscow Institute of Electronics and Mathematics, 101000 Moscow (Russian Federation); P.L. Kapitza Institute for Physical Problems RAS , Moscow 119334 (Russian Federation); Lehtinen, J.S. [VTT Technical Research Centre of Finland Ltd., Centre for Metrology MIKES, P.O. Box 1000, FI-02044 VTT (Finland)

    2017-02-15

    Highlights: • Junctionless Cooper pair box. • Quantum phase slips. • Coulomb blockade and gate modulation of the Coulomb gap. - Abstract: Quantum phase slip (QPS) is the topological singularity of the complex order parameter of a quasi-one-dimensional superconductor: momentary zeroing of the modulus and simultaneous 'slip' of the phase by ±2π. The QPS event(s) are the dynamic equivalent of tunneling through a conventional Josephson junction containing static in space and time weak link(s). Here we demonstrate the operation of a superconducting single electron transistor (Cooper pair transistor) without any tunnel junctions. Instead a pair of thin superconducting titanium wires in QPS regime was used. The current–voltage characteristics demonstrate the clear Coulomb blockade with magnitude of the Coulomb gap modulated by the gate potential. The Coulomb blockade disappears above the critical temperature, and at low temperatures can be suppressed by strong magnetic field.

  17. Cooperative Retransmissions Through Collisions

    CERN Document Server

    Qureshi, Jalaluddin; Foh, Chuan Heng

    2011-01-01

    Interference in wireless networks is one of the key capacity-limiting factors. Recently developed interference-embracing techniques show promising performance on turning collisions into useful transmissions. However, the interference-embracing techniques are hard to apply in practical applications due to their strict requirements. In this paper, we consider utilising the interference-embracing techniques in a common scenario of two interfering sender-receiver pairs. By employing opportunistic listening and analog network coding (ANC), we show that compared to traditional ARQ retransmission, a higher retransmission throughput can be achieved by allowing two interfering senders to cooperatively retransmit selected lost packets at the same time. This simultaneous retransmission is facilitated by a simple handshaking procedure without introducing additional overhead. Simulation results demonstrate the superior performance of the proposed cooperative retransmission.

  18. Cooperative Learning i voksenundervisningen

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne

    Nationalt Center for Kompetenceudvikling har evalueret undervisningsmetoden Cooperative Learning i voksenundervisningen og dokumenteret positive effekter på oplevelsen af samarbejde og på lærere og kursisters engagement - men har ikke kunnet påvise systematiske positive effekter af metoden på...... kursisters frafald, fravær og karakterer. Projektet har afprøvet og videreudviklet den pædagogiske metode Cooperative Learning (CL) i en dansk virkelighed og mere specifikt i forhold til VUC'ernes nye kursistgrupper med det overordnede mål at øge gennemførslen markant og målbart ved at anvende og udvikle en...

  19. Cooperation or Silent Rivalry?

    DEFF Research Database (Denmark)

    Zank, Wolfgang

    2010-01-01

    For decades the US has had a hegemonic position in the Middle East. A key country in this respect has been Egypt. However, in recent decades the EU has made itself increasingly felt in the region. Due to enlargements the EU came geographically much closer, and the Internal Market has generated...... a gravitational pull which goes beyond economic problems. Furthermore, the EU has gradually built up a coherent policy on many fields. The EU has become the “reform anchor” and most important cooperation partner for Egypt. The progress towards increasing Egypt’s “Stake in the Internal Market” places cooperation...... to see the US and EU as rivals. Their roles are rather complementary. The article explores developments in a long-term perspective. Internal and structural developments have had a heavy impact, but at important junctions ideas and strategies for gaining political legitimacy were powerful factors too...

  20. Binding of AR to SMRT/N-CoR complex and its co-operation with PSA promoter in prostate cancer cells treated with natural histone deacetylase inhibitor NaB.

    Science.gov (United States)

    Trtkova, K; Paskova, L; Matijescukova, N; Strnad, M; Kolar, Z

    2010-01-01

    Signaling through the androgen receptor (AR) plays a critical role in prostate cancer progression. The AR is a classical nuclear receptor (NR) providing a link between signaling molecule and transcription response. Histone deacetylase inhibitors- (HDACI) have antiproliferative and proapoptotic effects on prostate cancer cells and their implication in silence AR signaling may have potential therapeutic use. We aimed to study the inhibitory effects of the corepressor SMRT (Silencing Mediator for Retinoid and Thyroid -hormone receptors) which forms a complex together with nuclear receptor corepressor (N-CoR) and with histone deacetylase 3 (HDAC3) on AR activity.The androgen-sensitive prostate cancer cell line LNCaP and androgen-insensitive prostate cancer cell line C4-2 both AR-positive, and androgen-insensitive DU145 and PC3 prostate cancer cell lines were treated with two HDACIs, sodium butyrate (NaB) and/or trichostatin A (TSA). We amplified immunoprecipitated DNA by conventional PCR and in the -following step we used the chromatin immunoprecipitation (ChIP) analysis coupled with quantitative PCR for monitoring NaB induced formation of AR-SMRT/N-CoR complex binding on the PSA promoter. The co-immunoprecipitation assay revealed increase in AR-SMRT formation in NaB treated cells. Simultaneously, the Western blot analysis showed a significant decrease in AR protein expression. In conclusion, the inhibitory effect of NaB on AR gene expression seems to be specific and unique for prostate cancer AR-positive cell lines and corresponds with its ability to stimulate AR-SMRT complex formation. We suggest that AR and SMRT/N-CoR corepressors may form a stable complex in vitro and NaB may facilitate the interaction between AR nuclear steroid receptor and SMRT corepressor prote.