Science.gov

Sample records for positive co-operative activity

  1. Fostering Positive Peer Relations in the Primary Classroom through Circle Time and Co-Operative Games

    ERIC Educational Resources Information Center

    Mary, Latisha

    2014-01-01

    The aim of this study was to investigate the role of co-operative games and circle time activities in fostering positive peer relations in two French Primary classrooms (N = 40). It presents French teachers' and pupils' perceptions of a set of co-operative games and circle time activities implemented within a year long study on personal,…

  2. Co-operation at work: a process-oriented perspective on joint activity in inter-organizational relations.

    PubMed

    Wehner, T; Clases, C; Bachmann, R

    2000-07-01

    In this paper the authors present a conceptual framework for analysing co-operation between organizations as a situated process, highlighting co-operation, co-ordination and co-construction as different modes of joint activity. Within this framework, the analysis of unexpected events becomes a crucial issue. The analytic power of reconstructing the (psycho-) logics of unexpected events in inter-organizational relations will be demonstrated in the presentation of selected outcomes of a research project on the dynamics of producer-supplier relationships in the German automobile industry. Also in this empirical part, the significance of trust and confidence in inter-organizational relations will be reflected. PMID:10929832

  3. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    PubMed Central

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  4. Co-Operative Education or Co-Operative Placement?

    ERIC Educational Resources Information Center

    Dickson, C. R.

    The Co-operative Education Department at Mohawk College is designed to extend the academic learning process into the workplace through on-the-job learning experiences which enhance the students' vocational maturation and personal development, and are integrated with the learning objectives of the program. The department offers paid, supervised…

  5. It All Began with Raiffeisen: Co-operatives as Instruments of Self-Help and Development.

    ERIC Educational Resources Information Center

    Nover, Kurt

    1986-01-01

    The rural and manufacturing co-operatives and credit co-operatives in the Federal Republic of Germany have succeeded in continuously expanding and consolidating their position within the framework of the country's market economy. As the biggest organizations of medium-size enterprises, the co-operatives have adapted to the new circumstances…

  6. Optical positions of active galaxies

    NASA Astrophysics Data System (ADS)

    Meurs, E. J. A.

    1984-04-01

    Optical positions are calculated for 26 active galaxies (mainly Markarian dn Arakelian objects), using the plate-measuring apparatus at Leiden Observatory on the O plates of the Palomar Sky Survey and applying AGK-3 data in the reductions. The results are presented in a table and have accuracy 0.5 arcsec; a comparison with the positions determined by Clements (1981, 1983) for 19 objects reveals a possible offset of -0.28 arcsec in the right-ascension determinations.

  7. The Co-Operative: Good with Schools?

    ERIC Educational Resources Information Center

    Coates, Max

    2015-01-01

    The article is a summary of a small-scale research project which considers the formation of Co-operative Trust Schools. This was carried out in 2013 at a time when the number of schools becoming Academies and Trust Schools through the Co-operative College was burgeoning. Through questionnaire, interview, documentary analysis and exploration of…

  8. Women and International Intellectual Co-Operation

    ERIC Educational Resources Information Center

    Goodman, Joyce

    2012-01-01

    The article explores ways in which intellectual co-operation at the League of Nations [SDN] provided a space for the engagement of culturally elite women in intellectual co-operation circles in Geneva, Paris and a range of national contexts stretching across Europe, Latin America and Asia. It discusses the language of the "international mind" and…

  9. Making Co-Operative Ideas Work

    ERIC Educational Resources Information Center

    Arnold, Phil

    2013-01-01

    Reddish Vale Technology College was the first co-operative trust in England. The democratic and co-operative nature of the experiment mean that students have gained a greater voice in the organisation of the school. As a result, new social enterprises, environmental interventions, connections with the community and with the wider co-operative…

  10. [SUPPORT, CO-OPERATIVE EDUCATION PROGRAMMES, PRAGMATIC CODE OF ETHICS: A CLINICAL APPROACH OF EXECUTIVE TRAINING].

    PubMed

    Cabaret, Véronique

    2016-01-01

    This article aims at introducing an educational sequence completed at l'Institut de Formation des Cadres de Santé (IFCS) at the CHRU in Lille in France, entitled "training project and educational project" present in the "training duties" module whose goal is to generate students'knowledge through co-operative education programmes. By creating this innovative sequence, the educational aim is to use the Institut ground as a ground of learning, associated with the various internship grounds, in order to get the most of co-operative education programmes. Besides, in a pragmatic code of ethics in training, the teaching staff draw their inspiration from a clinical approach of executive training: they regard students as true protagonists in a co-operative plan created for them, wishing to design it with them using their words. Thus, students are brought to criticize the IFCS educational project and debate it with the trainers who have built it. Each partner tries to understand the Other, being aware of their being different. By contributing every year to rewriting the educational project which directly concerns them, students build their professional positions as health executives. They play an active role in co-operative education programmes just like IFCS outside partners. PMID:27305794

  11. Making poverty history in Sandwell the co-operative way.

    PubMed

    Mooney, Mary

    2008-01-01

    The purpose of this paper is to demonstrate how a financial cooperative, owned and managed at a local level, can have a positive impact on financial exclusion. Member-owners of the co-operative are able to access easy saving products, take advantage of affordable loans, and develop transferable skills working as volunteers at the strategic and community level. PMID:18771197

  12. Co-operativity in a nanocrystalline solid-state transition

    NASA Astrophysics Data System (ADS)

    White, Sarah L.; Smith, Jeremy G.; Behl, Mayank; Jain, Prashant K.

    2013-12-01

    Co-operativity is a remarkable phenomenon mostly seen in biology, where initial reaction events significantly alter the propensity of subsequent reaction events, giving rise to a nonlinear tightly regulated synergistic response. Here we have found unique evidence of atomic level co-operativity in an inorganic material. A thousand-atom nanocrystal (NC) of the inorganic solid cadmium selenide exhibits strong positive co-operativity in its reaction with copper ions. A NC doped with a few copper impurities becomes highly prone to be doped even further, driving an abrupt transition of the entire NC to the copper selenide phase, as manifested by a strongly sigmoidal response in optical spectroscopy and electron diffraction measurements. The examples presented here suggest that cooperative phenomena may have an important role in the solid state, especially in the nucleation of new chemical phases, crystal growth, and other materials’ transformations.

  13. Co-operativity in a nanocrystalline solid-state transition.

    PubMed

    White, Sarah L; Smith, Jeremy G; Behl, Mayank; Jain, Prashant K

    2013-01-01

    Co-operativity is a remarkable phenomenon mostly seen in biology, where initial reaction events significantly alter the propensity of subsequent reaction events, giving rise to a nonlinear tightly regulated synergistic response. Here we have found unique evidence of atomic level co-operativity in an inorganic material. A thousand-atom nanocrystal (NC) of the inorganic solid cadmium selenide exhibits strong positive co-operativity in its reaction with copper ions. A NC doped with a few copper impurities becomes highly prone to be doped even further, driving an abrupt transition of the entire NC to the copper selenide phase, as manifested by a strongly sigmoidal response in optical spectroscopy and electron diffraction measurements. The examples presented here suggest that cooperative phenomena may have an important role in the solid state, especially in the nucleation of new chemical phases, crystal growth, and other materials' transformations. PMID:24335761

  14. Analysis and Prospects of European Co-Operation in the Field of Regional Planning. Activity Report of the Committee of Senior Officials 1976-1978.

    ERIC Educational Resources Information Center

    Council of Europe, Strasbourg (France).

    To guide future work, to provide an overall view of the program of technical cooperation in regional planning, and to form a basis for a Conference Ministerial Resolution, the report outlines the activities of the Committee of Senior Officials (CSO) of the Council of Europe's Conference of Ministers Responsible for Regional Planning during…

  15. 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.

    PubMed Central

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

    2002-01-01

    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. PMID:12133007

  16. 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.

    PubMed

    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. PMID:12133007

  17. The Discourse Co-operation Test.

    ERIC Educational Resources Information Center

    Friel, Michael

    1984-01-01

    Proposes a new type of oral test, based on Grice's Co-operative Principle and its dependent maxims, to measure communicative competence. Describes the design, administration, and scoring of this timed, multiple-choice test and gives sample test materials. Discusses applications to testing languages for special purposes and ways of presenting the…

  18. INTERNATIONAL CO-OPERATION IN NUCLEAR DATA EVALUATION

    SciTech Connect

    Herman, M.; Katakura,J.; Koning,A.; Nordborg,C.

    2010-04-30

    The OECD Nuclear Energy Agency (NEA) is organising a co-operation between the major nuclear data evaluation projects in the world. The co-operation involves the ENDF, JEFF, and JENDL projects, and, owing to the collaboration with the International Atomic Energy Agency (IAEA), also the Russian RUSFOND and the Chinese CENDL projects. The Working Party on international nuclear data Evaluation Cooperation (WPEC), comprised of about 20 core members, manages this co-operation and meets annually to discuss progress in each evaluation project and also related experimental activities. The WPEC assesses common needs for nuclear data improvements and these needs are then addressed by initiating joint evaluation efforts. The work is performed in specially established subgroups, consisting of experts from the participating evaluation projects. The outcome of these subgroups is published in reports, issued by the NEA. Current WPEC activities comprise for example a number of studies related to nuclear data uncertainties, including a review of methods for the combined use of integral experiments and covariance data, as well as evaluations of some of the major actinides, such as {sup 235}U and {sup 239}Pu. This paper gives an overview of current and planned activities within the WPEC.

  19. Quorum sensing protects bacterial co-operation from exploitation by cheats

    PubMed Central

    Allen, Richard C; McNally, Luke; Popat, Roman; Brown, Sam P

    2016-01-01

    Quorum sensing (QS) is a cell–cell communication system found in many bacterial species, commonly controlling secreted co-operative traits, including extracellular digestive enzymes. We show that the canonical QS regulatory architecture allows bacteria to sense the genotypic composition of high-density populations, and limit co-operative investments to social environments enriched for co-operators. Using high-density populations of the opportunistic pathogen Pseudomonas aeruginosa we map per-capita signal and co-operative enzyme investment in the wild type as a function of the frequency of non-responder cheats. We demonstrate mathematically and experimentally that the observed response rule of ‘co-operate when surrounded by co-operators' allows bacteria to match their investment in co-operation to the composition of the group, therefore allowing the maintenance of co-operation at lower levels of population structuring (that is, lower relatedness). Similar behavioural responses have been described in vertebrates under the banner of ‘generalised reciprocity'. Our results suggest that mechanisms of reciprocity are not confined to taxa with advanced cognition, and can be implemented at the cellular level via positive feedback circuits. PMID:26744811

  20. Quorum sensing protects bacterial co-operation from exploitation by cheats.

    PubMed

    Allen, Richard C; McNally, Luke; Popat, Roman; Brown, Sam P

    2016-07-01

    Quorum sensing (QS) is a cell-cell communication system found in many bacterial species, commonly controlling secreted co-operative traits, including extracellular digestive enzymes. We show that the canonical QS regulatory architecture allows bacteria to sense the genotypic composition of high-density populations, and limit co-operative investments to social environments enriched for co-operators. Using high-density populations of the opportunistic pathogen Pseudomonas aeruginosa we map per-capita signal and co-operative enzyme investment in the wild type as a function of the frequency of non-responder cheats. We demonstrate mathematically and experimentally that the observed response rule of 'co-operate when surrounded by co-operators' allows bacteria to match their investment in co-operation to the composition of the group, therefore allowing the maintenance of co-operation at lower levels of population structuring (that is, lower relatedness). Similar behavioural responses have been described in vertebrates under the banner of 'generalised reciprocity'. Our results suggest that mechanisms of reciprocity are not confined to taxa with advanced cognition, and can be implemented at the cellular level via positive feedback circuits. PMID:26744811

  1. Co-Operation: The Antidote to Isolated Misery

    ERIC Educational Resources Information Center

    Jones, Sarah

    2013-01-01

    This is a case study demonstrating the impact the co-operative movement has had on one co-operative school in south-west England. Lipson Co-operative Academy in Plymouth was one of the first schools to convert to become a co-operative school in 2009. The article has been co-written by members of the Academy and focuses on three transformational…

  2. Position Statement on Active Outdoor Play

    PubMed Central

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N = 9) and cross-sectorial individuals/organizations (N = 17), and an extensive stakeholder consultation process (N = 1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: “Access to active play in nature and outdoors—with its risks— is essential for healthy child development. We recommend increasing children’s opportunities for self-directed play outdoors in all settings—at home, at school, in child care, the community and nature.” The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development. PMID:26062040

  3. Position Statement on Active Outdoor Play.

    PubMed

    Tremblay, Mark S; Gray, Casey; Babcock, Shawna; Barnes, Joel; Bradstreet, Christa Costas; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-06-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3-12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N=9) and cross-sectorial individuals/organizations (N=17), and an extensive stakeholder consultation process (N=1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: "Access to active play in nature and outdoors--with its risks--is essential for healthy child development. We recommend increasing children's opportunities for self-directed play outdoors in all settings--at home, at school, in child care, the community and nature." The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development. PMID:26062040

  4. Sixteen Years of International Co-operation. The OECD/NEA Co-operative Programme on Decommissioning

    SciTech Connect

    Menon, S.; Valencia, L.

    2002-02-25

    The Co-operative Programme on Decommissioning under the administration of the Radioactive Waste Management Committee of the OECD Nuclear Energy Agency (NEA) has recently completed sixteen years of operation. The Programme, which is essentially an information exchange programme between decommissioning projects, came into being in 1985. It has grown from an initial 10 decommissioning projects from 7 countries to 39 projects from 14 countries today. From purely information exchange to start with, the Programme has, in later years, been functioning as a voice for the collective expression of views of the implementers of nuclear decommissioning. During the first sixteen years of the operation of the Co-operative Programme, nuclear decommissioning has grown from local specialist activities within projects to a competitive commercial industry. By the dismantling and release from regulatory control of over a dozen diverse nuclear facilities, the Programme has been able to demonstrate in practice, that nuclear decommissioning can be performed safely both for the workers and the public, and that this can be done at reasonable costs in an environmentally friendly fashion. During the recent years, discussions and work within the Co-operative Programme, specially within some of the Task Groups, have had/are having effects and repercussions not just in the field of nuclear decommissioning, but can possibly affect activities and regulations in other industries. This paper describes how the Programme and its activities and procedures have evolved over the years and indicate the directions of developments in the organization and execution of decommissioning projects. Finally, it gives a brief overview of the achievements of the Cooperative Programme and visualizes future developments in the field of nuclear decommissioning.

  5. Discursive Positionings and Emotions in Modelling Activities

    ERIC Educational Resources Information Center

    Daher, Wajeeh

    2015-01-01

    Mathematical modelling is suggested as an activity through which students engage in meaningful mathematics. In the current research, the modelling activity of a group of four seventh-grade students was analysed using the discursive analysis framework. The research findings show that the positionings and emotions of the group members during their…

  6. Discursive positionings and emotions in modelling activities

    NASA Astrophysics Data System (ADS)

    Daher, Wajeeh

    2015-11-01

    Mathematical modelling is suggested as an activity through which students engage in meaningful mathematics. In the current research, the modelling activity of a group of four seventh-grade students was analysed using the discursive analysis framework. The research findings show that the positionings and emotions of the group members during their participation in the modelling activity changed as the activity proceeded. Overall, it can be said that three of the four group members acted as insiders, while the fourth acted as an outsider, and only, towards the end of the group's work on the activity, he acted as an insider. Moreover, the research findings point at four factors that affected the group members' positionings and emotions during the modelling activity: the member's characteristics, the member's history of learning experiences, the activity characteristics and the modelling phases. Furthermore, the different positionings of the group members in the different modelling phases were accompanied by different emotions experienced by them, where being an insider and a collaborator resulted in positive emotions, while being an outsider resulted in negative emotions.

  7. Adenosinergic Immunosuppression by Human Mesenchymal Stromal Cells Requires Co-Operation with T cells.

    PubMed

    Kerkelä, Erja; Laitinen, Anita; Räbinä, Jarkko; Valkonen, Sami; Takatalo, Maarit; Larjo, Antti; Veijola, Johanna; Lampinen, Milla; Siljander, Pia; Lehenkari, Petri; Alfthan, Kaija; Laitinen, Saara

    2016-03-01

    Mesenchymal stem/stromal cells (MSCs) have the capacity to counteract excessive inflammatory responses. MSCs possess a range of immunomodulatory mechanisms, which can be deployed in response to signals in a particular environment and in concert with other immune cells. One immunosuppressive mechanism, not so well-known in MSCs, is mediated via adenosinergic pathway by ectonucleotidases CD73 and CD39. In this study, we demonstrate that adenosine is actively produced from adenosine 5'-monophosphate (AMP) by CD73 on MSCs and MSC-derived extracellular vesicles (EVs). Our results indicate that although MSCs express CD39 at low level and it colocalizes with CD73 in bulge areas of membranes, the most efficient adenosine production from adenosine 5'-triphosphate (ATP) requires co-operation of MSCs and activated T cells. Highly CD39 expressing activated T cells produce AMP from ATP and MSCs produce adenosine from AMP via CD73 activity. Furthermore, adenosinergic signaling plays a role in suppression of T cell proliferation in vitro. In conclusion, this study shows that adenosinergic signaling is an important immunoregulatory mechanism of MSCs, especially in situations where ATP is present in the extracellular environment, like in tissue injury. An efficient production of immunosuppressive adenosine is dependent on the concerted action of CD39-positive immune cells with CD73-positive cells such as MSCs or their EVs. Stem Cells 2016;34:781-790. PMID:26731338

  8. Are University Co-Operative Education Students Safe? Perceptions of Risk to Students on Work Terms

    ERIC Educational Resources Information Center

    Newhook, Rebecca

    2016-01-01

    As students venture off campus for university-sponsored activities, are they at risk, given that universities are better able to control risk factors on campus than they can for their off-campus activities? Co-operative education is a formalized and longstanding academic program that often sees students spend upwards of a third of their time off…

  9. Co-operation between patient organisations and the drug industry in Finland.

    PubMed

    Hemminki, Elina; Toiviainen, Hanna K; Vuorenkoski, Lauri

    2010-04-01

    The aim of the study was to investigate the co-operation between patient organizations and the drug industry in Finland prior to critical discussions on the topic. The data were gathered by a questionnaire survey of 85 patient organisations (response rate 65%, n = 55) and 20 drug firms (response rate 100%) in 2003, and by interviewing 13 organisations and surveying their web-pages and other documents in 2004. In the surveys, half of the patient organisations and 80% of the drug firms considered co-operation important. Most (71%) organisations reported financial support from the drug industry. Most organisations and drug firms had experienced problems. Common problems for organisations were too little or too unpredictable support from industry, and threats to independence and objectivity. Drug firms frequently mentioned unclear rules of co-operation. The patient organisation interviews exhibited similar themes and findings to those found in the surveys, revealing the complexity and importance of co-operation in organisation activities, and the variation between organisations. This case study from Finland showed that co-operation between patient organizations and the drug industry was common, many-sided and not usually transparent. The close connections between patient organizations and commercial companies, particularly drug firms, raise several policy issues and the need for action. PMID:20163903

  10. Benzoyl peroxide interferes with metabolic co-operation between cultured human epidermal keratinocytes

    SciTech Connect

    Lawrence, N.J.; Parkinson, E.K.; Emmerson, A.

    1984-03-01

    The ability of benzoyl peroxide to inhibit metabolic co-operation in rodent cell cultures may be relevant to its recently reported tumour promoting activity in mouse epidermis. We show here that non-toxic doses of this compound reduce metabolic co-operation between human epidermal keratinocytes to approximately 30% of that found in controls. The doses of benzoyl peroxide used did not affect keratinocyte morphology or their rate of attachment to the culture substratum. These results could be important as benzoyl peroxide is widely used in industry.

  11. Computer-Supported Co-operative Learning.

    ERIC Educational Resources Information Center

    Florea, Adina Magda

    1998-01-01

    Discusses the impact of computer-supported cooperative work tools in the creation of educational environments and the facilities such tools bring to teaching methods, and examines the relationship between new techniques and the learner-centered, active learning approach in higher education. The importance of collaborative learning in this context…

  12. Council for Cultural Co-Operation and Cultural Fund. Annual Report 1972.

    ERIC Educational Resources Information Center

    Council for Cultural Cooperation, Strasbourg (France).

    This document is a report on the activities of the Council for Cultural Co-Operation (CCC) and Cultural Fund for 1972. The CCC is briefly defined as being designed to reinforce educational and cultural cooperation among the 21 countries of the CCC, especially in matters of research, information, and documentation. The document is composed of…

  13. Cyberethics and co-operation in the information society.

    PubMed

    Fuchs, Christian; Bichler, Robert M; Raffl, Celina

    2009-12-01

    The task of this paper is to ground the notion of cyberethics of co-operation. The evolution of modern society has resulted in a shift from industrial society towards informational capitalism. This transformation is a multidimensional shift that affects all aspects of society. Hence also the ethical system of society is penetrated by the emergence of the knowledge society and ethical guidelines for the information age are needed. Ethical issues and conflicts in the knowledge society are connected to topics of ecological and social sustainability. For information ethics and cyberethics, the sustainable design of society, social, and socio-technological systems is important. In this context the notions of sustainability and co-operation are discussed. Based on these categories, the approach of cyberethics of co-operation can be theoretically grounded. PMID:19440854

  14. SMEs and their co-operation with academia.

    PubMed

    Antoine, Jean Michel; Strömqvist, Mats

    2005-01-01

    Co-operation between SMEs and Academia can be a win-win situation when each partner understands the constraints of the other. SMEs are often leaders in innovation; therefore more ready to share interest in research. They are flexible and dynamic. They need a short feed-back to sustain their co-operation. Academia is often more long-term oriented and more question- than answer-oriented. A code of conduct can ease the relationship because it can anticipate the potential problems. PMID:16137116

  15. Co-Operative Training in the Sheffield Forging Industry

    ERIC Educational Resources Information Center

    Duncan, R.

    2008-01-01

    Purpose: The purpose of this paper is to give details of an operation carried out in Sheffield to increase the recruitment of young men into the steel forging industry. Design/methodology/approach: The Sheffield Forges Co-operative Training Scheme was designed to encourage boys to enter the forging industry and to provide them with training and…

  16. Supersurveillance, Democracy, and Co-Operation--The Challenge for Teachers

    ERIC Educational Resources Information Center

    Schostak, John

    2014-01-01

    The paper explores pedagogies of surveillance and counter pedagogies of radical democracy and co-operative practice and their implications for continuing professional development (CPD). Teachers have had to respond to an increasing naturalisation of surveillance in schools. However, this naturalisation can be countered by drawing upon the emergent…

  17. Securing co-operation from persons supplying statistical data

    PubMed Central

    Aubenque, M. J.; Blaikley, R. M.; Harris, F. Fraser; Lal, R. B.; Neurdenburg, M. G.; Hernández, R. de Shelly

    1954-01-01

    Securing the co-operation of persons supplying information required for medical statistics is essentially a problem in human relations, and an understanding of the motivations, attitudes, and behaviour of the respondents is necessary. Before any new statistical survey is undertaken, it is suggested by Aubenque and Harris that a preliminary review be made so that the maximum use is made of existing information. Care should also be taken not to burden respondents with an overloaded questionnaire. Aubenque and Harris recommend simplified reporting. Complete population coverage is not necessary. Neurdenburg suggests that the co-operation and support of such organizations as medical associations and social security boards are important and that propaganda should be directed specifically to the groups whose co-operation is sought. Informal personal contacts are valuable and desirable, according to Blaikley, but may have adverse effects if the right kind of approach is not made. Financial payments as an incentive in securing co-operation are opposed by Neurdenburg, who proposes that only postage-free envelopes or similar small favours be granted. Blaikley and Harris, on the other hand, express the view that financial incentives may do much to gain the support of those required to furnish data; there are, however, other incentives, and full use should be made of the natural inclinations of respondents. Compulsion may be necessary in certain instances, but administrative rather than statutory measures should be adopted. Penalties, according to Aubenque, should be inflicted only when justified by imperative health requirements. The results of surveys should be made available as soon as possible to those who co-operated, and Aubenque and Harris point out that they should also be of practical value to the suppliers of the information. Greater co-operation can be secured from medical persons who have an understanding of the statistical principles involved; Aubenque and

  18. Comprehensive School Physical Activity Programs. Position Statement

    ERIC Educational Resources Information Center

    National Association for Sport and Physical Education, 2008

    2008-01-01

    The National Association for Sport and Physical Education (NASPE) recommends that all PK-12 schools implement a Comprehensive School Physical Activity Program. Schools play an important role in public health, and the physical, mental, and social benefits of regular physical activity for youth are well documented. Leading public health, medical,…

  19. Interdisciplinary Co-operation (Part II of "Language Learning: Individual Needs, Interdisciplinary Co-operation, Bi- and Multilingualism").

    ERIC Educational Resources Information Center

    1978

    The following papers on interdisciplinary cooperation in second language instruction are included: (1) "Language Teaching: Possibilities for Interdisciplinary Co-operation," by James E. Alatis; (2) "L'insegnamento della letteratura italiana (The Teaching of Italian Literature)," by Ezio Raimondi; (3) "Objective Evaluation and Transparency," by…

  20. Vitrification assistance program: international co-operation on vitrification technology

    SciTech Connect

    Penrice, Ch.; McGowan, B.; Garth, B.; Reed, J.; Prod'homme, A.; Sartelet, S.; Guerif, H.N.; Hollebecque, J.F.; Flament, T.; Prod'homme, A.

    2008-07-01

    With 10 vitrification lines in operation (3 on WVP in Sellafield, 1 on AVM in Marcoule and 6 on AVH in La Hague), Sellafield Ltd and Areva NC benefit from the most in-depth experience worldwide in the vitrification of highly active liquors within a framework of commercial operations. Based on the two-step process design, using a calciner and an induction-heated hot melter, which was initially deployed in Marcoule in 1978, core vitrification equipment has been continuously improved by the independent development programmes of the two companies. In March 2005, Sellafield Ltd and Areva NC signed the Vitrification Assistance Program (hereafter referred to as VAP); a co-operative project lasting 4 years during which Areva NC is to share some areas of their experience and expertise with Sellafield Ltd. Now at the halfway point of this project, this paper summarises the work performed by the VAP team to date, highlighting the early benefits and lessons learned. The following points will be developed: - Equipment delivery and preparation for implementation on WVP - Training organization and dissemination to WVP teams - Lessons learned from the early changes implemented in operations (Calciner, Melter, Dust Scrubber and Primary off gas system), and initial feedback from the first campaign using a VAP equipped line. In conclusion: The vitrification process and technology implemented at Sellafield and at La Hague, based on the two-step process, have proved to be efficient in treating high active liquor of various types. Ten lines based on this principle have been successfully operated for more than 15 years in France and in the UK. The process has also been demonstrated to be sufficiently versatile to benefit from continuous improvement and development programmes. VAP, as a complete package to support vitrification technology and knowledge transfer from AREVA NC to Sellafield Ltd, has provided the framework for fruitful technical exchanges and discussions between the two

  1. Action by the Customs Co-operation Council to combat illicit drug trafficking.

    PubMed

    Gotschlich, G D

    1983-01-01

    Since its establishment in 1953, the Customs Co-operation Council (CCC) has been actively involved in combating illicit drug trafficking. CCC has adopted legal measures designed to meet the requirements of member States in their efforts to promote the prevention, investigation and repression of customs offences, including drug smuggling. CCC studies patterns and trends in drug trafficking and promotes ways and means of detecting drug smuggling and financial transactions related to such smuggling. CCC publishes studies and handbooks that serve as practical guides to national customs administrations of member States. In its work to combat drug trafficking, the CCC co-operates with the United Nations bodies concerned with drug control and the International Criminal Police Organizations (ICPO/Interpol). PMID:6563930

  2. Associations among positive mood, brain, and cardiovascular activities in an affectively positive situation.

    PubMed

    Matsunaga, Masahiro; Isowa, Tokiko; Kimura, Kenta; Miyakoshi, Makoto; Kanayama, Noriaki; Murakami, Hiroki; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Konagaya, Toshihiro; Kaneko, Hiroshi; Ohira, Hideki

    2009-03-31

    It is hypothesized that experiencing positive emotions such as pleasure leads to a perception of the body being in a positive state. This study demonstrated associations among positive mood, brain, and cardiovascular activities by simultaneously recording these activities when positive emotions were evoked in participants watching films revolving around a love story. Heart rate variability analysis revealed increased parasympathetic nervous activity while watching the film. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, superior temporal gyrus, inferior frontal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with subjective positive mood. Activities of brain regions considered to be related to interoceptive awareness, such as the insular cortex, anterior cingulate cortex, amygdala, and orbitofrontal cortex, were also temporally associated with the cardiovascular change. These results suggest that while an individual experiences positive emotions, activities of the central nervous system and cardiovascular system may be interrelated, and the brain may perceive the body to be in a positive state. PMID:19368841

  3. Generalized microscopic reversibility, kinetic co-operativity of enzymes and evolution.

    PubMed Central

    Ricard, J

    1978-01-01

    Generalized microscopic reversibility implies that the apparent rate of any catalytic process in a complex mechanism is paralleled by substrate desorption in such a way that this ratio is held constant within the reaction mechanism [Whitehead (1976) Biochem. J. 159, 449--456]. The physical and evolutionary significances of this concept, for both polymeric and monomeric enzymes, are discussed. For polymeric enzymes, generalized microscopic reversibility of necessity occurs if, within the same reaction sequence, the substrate stabilizes one type of conformation of the active site only. Generalized microscopic reversibility suppresses the kinetic co-operativity of the slow transition model [Ainslie, Shill & Neet (1972) J. Biol. Chem. 247, 7088--7096]. This situation is obtained if the free-energy difference between the corresponding transition states of the two enzyme forms is held constant along the reaction co-ordinate. This situation implies that the 'extra costs' of energy (required to pass each energy barrier) that are not covered by the corresponding binding energies of the transition states vary in a similar way along the two reaction co-ordinates. The regulatory behaviour of monomeric enzymes is discussed in the light of the concept of 'catalytic perfection' proposed by Albery & Knowles [(1976) Biochemistry 15, 5631--5640]. These authors claim that an enzyme will be catalytically 'perfect' when its catalytic efficiency is maximum. If this situation occurs for a monomeric enzyme obeying either the slow transition or the mnemonical model, it can be shown that the kinetic co-operativity disappears. In other words, kinetic co-operativity of a monomeric enzyme is 'paid for' at the expense of catalytic efficiency, and the monomeric enzyme cannot be simultaneously co-operative and catalytically very efficient. This is precisely what has been found experimentally in a number of cases. PMID:743234

  4. Releasing the brakes in coagulation Factor IXa by co-operative maturation of the substrate-binding site.

    PubMed

    Kristensen, Line Hyltoft; Olsen, Ole H; Blouse, Grant E; Brandstetter, Hans

    2016-08-01

    Coagulation Factor IX is positioned at the merging point of the intrinsic and extrinsic blood coagulation cascades. Factor IXa (activated Factor IX) serves as the trigger for amplification of coagulation through formation of the so-called Xase complex, which is a ternary complex of Factor IXa, its substrate Factor X and the cofactor Factor VIIIa on the surface of activated platelets. Within the Xase complex the substrate turnover by Factor IXa is enhanced 200000-fold; however, the mechanistic and structural basis for this dramatic enhancement remains only partly understood. A multifaceted approach using enzymatic, biophysical and crystallographic methods to evaluate a key set of activity-enhanced Factor IXa variants has demonstrated a delicately balanced bidirectional network. Essential molecular interactions across multiple regions of the Factor IXa molecule co-operate in the maturation of the active site. This maturation is specifically facilitated by long-range communication through the Ile(212)-Ile(213) motif unique to Factor IXa and a flexibility of the 170-loop that is further dependent on the conformation in the Cys(168)-Cys(182) disulfide bond. Ultimately, the network consists of compensatory brakes (Val(16) and Ile(213)) and accelerators (Tyr(99) and Phe(174)) that together allow for a subtle fine-tuning of enzymatic activity. PMID:27208168

  5. Rhadinovirus Host Entry by Co-operative Infection

    PubMed Central

    May, Janet S.; Stevenson, Philip G.

    2015-01-01

    Rhadinoviruses establish chronic infections of clinical and economic importance. Several show respiratory transmission and cause lung pathologies. We used Murid Herpesvirus-4 (MuHV-4) to understand how rhadinovirus lung infection might work. A primary epithelial or B cell infection often is assumed. MuHV-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. While host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding target - and were infected poorly ex vivo. In situ analysis revealed that virions bound initially not to macrophages but to heparan+ type 1 alveolar epithelial cells (AECs). Although epithelial cell lines endocytose MuHV-4 readily in vitro, AECs did not. Rather bound virions were acquired by macrophages; epithelial infection occurred only later. Thus, host entry was co-operative - virion binding to epithelial cells licensed macrophage infection, and this in turn licensed AEC infection. An antibody block of epithelial cell binding failed to block host entry: opsonization provided merely another route to macrophages. By contrast an antibody block of membrane fusion was effective. Therefore co-operative infection extended viral tropism beyond the normal paradigm of a target cell infected readily in vitro; and macrophage involvement in host entry required neutralization to act down-stream of cell binding. PMID:25790477

  6. Nucleosome positioning and kinetics near transcription-start-site barriers are controlled by interplay between active remodeling and DNA sequence

    PubMed Central

    Parmar, Jyotsana J.; Marko, John F.; Padinhateeri, Ranjith

    2014-01-01

    We investigate how DNA sequence, ATP-dependent chromatin remodeling and nucleosome-depleted ‘barriers’ co-operate to determine the kinetics of nucleosome organization, in a stochastic model of nucleosome positioning and dynamics. We find that ‘statistical’ positioning of nucleosomes against ‘barriers’, hypothesized to control chromatin structure near transcription start sites, requires active remodeling and therefore cannot be described using equilibrium statistical mechanics. We show that, unlike steady-state occupancy, DNA site exposure kinetics near a barrier is dominated by DNA sequence rather than by proximity to the barrier itself. The timescale for formation of positioning patterns near barriers is proportional to the timescale for active nucleosome eviction. We also show that there are strong gene-to-gene variations in nucleosome positioning near barriers, which are eliminated by averaging over many genes. Our results suggest that measurement of nucleosome kinetics can reveal information about sequence-dependent regulation that is not apparent in steady-state nucleosome occupancy. PMID:24068556

  7. Activities for Teaching Positive Psychology: A Guide for Instructors

    ERIC Educational Resources Information Center

    Froh, Jeffrey J., Ed.; Parks, Acacia C., Ed.

    2012-01-01

    Positive psychology is a rapidly expanding area of study that is of great interest to students at the graduate, undergraduate, and high school levels. But the field is so broad that teachers who want to cover all the bases when designing a positive psychology course may have difficulty locating and selecting materials. "Activities for Teaching…

  8. Active control of a flexible structure using a modal positive position feedback controller

    NASA Technical Reports Server (NTRS)

    Poh, S.; Baz, A.

    1990-01-01

    The feasibility of a new Modal Positive Position Feedback (MPPF) strategy in controlling the vibration of a complex flexible structure using a single piezo-electric active structural member is demonstrated. The control strategy generates its control forces by manipulating only the modal position signals of the structure to provide a damping action to undamped modes. This is in contrast to conventional modal controllers that rely in their operation on negative feedback of both the modal position and velocity. The proposed strategy is very simple to design and implement as it designs the controller at the uncoupled modal level and utilizes simple first order filters to achieve the Positive Position Feedback effect. The performance of the new strategy is enhanced by augmenting it with a time sharing strategy to share a small number of actuators between larger number of modes. The effectiveness of the new strategy is validated experimentally on a flexible box-type structure that has four bays and its first two bending modes are 2.015 and 6.535 Hz respectively. A single piezo-electric actuator is utilized as an active structural member to control several transverse bending modes of the structure. The performance of the active control system is determined in the time and the frequency domains. The results are compared with those obtained when using the Independent Modal Space Control (IMSC) of Meirovitch. The experimental results suggest the potential of the proposed strategy as a viable means for controlling the vibration of large flexible structures in real time.

  9. Active control of a flexible structure using a modal positive position feedback controller

    NASA Technical Reports Server (NTRS)

    Poh, S.; Baz, A.

    1990-01-01

    The feasibility of a new Modal Positive Position Feedback (MPPF) strategy in controlling the vibration of a complex flexible structure using a single piezo-electric active structural member is demonstrated. The control strategy generates its control forces by manipulating only the modal position signals of the structure to provide a damping action to undamped modes. This is in contrast to conventional modal controllers that rely in their operation on negative feedback of both the modal position and velocity. The proposed strategy is very simple to design and implement as it designs the controller at the uncoupled modal level and utilizes simple first order filters to achieve the Positive Position Feedback effect. The performance of the new strategy is enhanced by augmenting it with a time sharing strategy to share a small number of actuators between larger number of modes. The effectiveness of the new strategy is validated experimentally on a flexible box-type structure that has four bays and its first two bending modes are 2.015 and 6.535 Hz, respectively. A single piezo-electric actuator is utilized as an active structural member to control several transverse bending modes of the structure. The performance of the active control system is determined in the time and the frequency domains. The results are compared with those obtained when using the Independent Modal Space Control (IMSC) of Meirovitch. The experimental results suggest the potential of the proposed strategy as a viable means for controlling the vibration of large flexible structures in real time.

  10. Intramolecular signal transmission in enterobacterial aspartate transcarbamylases II. Engineering co-operativity and allosteric regulation in the aspartate transcarbamylase of Erwinia herbicola.

    PubMed

    Cunin, R; Rani, C S; Van Vliet, F; Wild, J R; Wales, M

    1999-12-17

    The aspartate transcarbamylase (ATCase) from Erwinia herbicola differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains ((c3)2(r2)3), as other enterobacterial ATCases and shows extensive primary structure conservation. In (c3)2(r2)3 ATCases, the association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. Alignment of the primary sequence of the regulatory polypeptides from the E. herbicola and from the paradigmatic Escherichia coli ATCases reveals major blocks of divergence, corresponding to discrete structural elements in the E. coli enzyme. Chimeric ATCases were constructed by exchanging these blocks of divergent sequence between these two ATCases. It was found that the amino acid composition of the outermost beta-strand of a five-stranded beta-sheet in the effector-binding domain of the regulatory polypeptide is responsible for the lack of co-operativity and response to ATP of the E. herbicola ATCase. A novel structural element involved in allosteric signal recognition and transmission in this family of ATCases was thus identified. PMID:10600394

  11. Effects of co-operative ligand binding on protein amide NH hydrogen exchange.

    PubMed

    Polshakov, Vladimir I; Birdsall, Berry; Feeney, James

    2006-03-01

    Amide protection factors have been determined from NMR measurements of hydrogen/deuterium amide NH exchange rates measured on assigned signals from Lactobacillus casei apo-DHFR and its binary and ternary complexes with trimethoprim (TMP), folinic acid and coenzymes (NADPH/NADP(+)). The substantial sizes of the residue-specific DeltaH and TDeltaS values for the opening/closing events in NH exchange for most of the measurable residues in apo-DHFR indicate that sub-global or global rather than local exchange mechanisms are usually involved. The amide groups of residues in helices and sheets are those most protected in apo-DHFR and its complexes, and the protection factors are generally related to the tightness of ligand binding. The effects of ligand binding that lead to changes in amide protection are not localised to specific binding sites but are spread throughout the structure via a network of intramolecular interactions. Although the increase in protein stability in the DHFR.TMP.NADPH complex involves increased ordering in the protein structure (requiring TDeltaS energy) this is recovered, to a large extent, by the stronger binding (enthalpic DeltaH) interactions made possible by the reduced motion in the protein. The ligand-induced protection effects in the ternary complexes DHFR.TMP.NADPH (large positive binding co-operativity) and DHFR.folinic acid.NADPH (large negative binding co-operativity) mirror the co-operative effects seen in the ligand binding. For the DHFR.TMP.NADPH complex, the ligand-induced protection factors result in DeltaDeltaG(o) values for many residues being larger than the DeltaDeltaG(o) values in the corresponding binary complexes. In contrast, for DHFR.folinic acid.NADPH, the DeltaDeltaG(o) values are generally smaller than many of those in the corresponding binary complexes. The results indicate that changes in protein conformational flexibility on formation of the ligand complex play an important role in determining the co-operativity in

  12. Position dependent rate dampening in any active hand controller

    NASA Technical Reports Server (NTRS)

    Gregory, William W. (Inventor); Kauffman, James W. (Inventor)

    1994-01-01

    A control system for an active hand controller, for example, uses a control stick connected to and controlled by a motor. Electronics are provided to control the motor to eliminate oscillations due to motor torque and high gain due to breakout at the control stick when the control stick is at about its null position. Both hardware as well as software implementations can provide position dependent dampening to the control sticks such that when the control stick is located about a null position, a higher rate of dampening is provided than when the control stick is located outside the null position, when a lower rate of dampening is provided. The system provides a stable active hand controller control stick without degraded force and feel characteristics of the system.

  13. A position-dependent transcription-activating domain in TFIIIA.

    PubMed

    Mao, X; Darby, M K

    1993-12-01

    Transcription of the Xenopus 5S RNA gene by RNA polymerase III requires the gene-specific factor TFIIIA. To identify domains within TFIIIA that are essential for transcriptional activation, we have expressed C-terminal deletion, substitution, and insertion mutants of TFIIIA in bacteria as fusions with maltose-binding protein (MBP). The MBP-TFIIIA fusion protein specifically binds to the 5S RNA gene internal control region and complements transcription in a TFIIIA-depleted oocyte nuclear extract. Random, cassette-mediated mutagenesis of the carboxyl region of TFIIIA, which is not required for promoter binding, has defined a 14-amino-acid region that is critical for transcriptional activation. In contrast to activators of RNA polymerase II, the activity of the TFIIIA activation domain is strikingly sensitive to its position relative to the DNA-binding domain. When the eight amino acids that separate the transcription-activating domain from the last zinc finger are deleted, transcriptional activity is lost. Surprisingly, diverse amino acids can replace these eight amino acids with restoration of full transcriptional activity, suggesting that the length and not the sequence of this region is important. Insertion of amino acids between the zinc finger region and the transcription-activating domain causes a reduction in transcription proportional to the number of amino acids introduced. We propose that to function, the transcription-activating domain of TFIIIA must be correctly positioned at a minimum distance from the DNA-binding domain. PMID:8246967

  14. Physical Activity Is Positively Associated with Episodic Memory in Aging

    PubMed Central

    Hayes, Scott M.; Alosco, Michael L.; Hayes, Jasmeet P.; Cadden, Margaret; Peterson, Kristina M.; Allsup, Kelly; Forman, Daniel E.; Sperling, Reisa A.; Verfaellie, Mieke

    2016-01-01

    Aging is associated with performance reductions in executive function and episodic memory, although there is substantial individual variability in cognition among older adults. One factor that may be positively associated with cognition in aging is physical activity. To date, few studies have objectively assessed physical activity in young and older adults, and examined whether physical activity is differentially associated with cognition in aging. Young (n = 29, age 18–31 years) and older adults (n = 31, ages 55–82 years) completed standardized neuropsychological testing to assess executive function and episodic memory capacities. An experimental face-name relational memory task was administered to augment assessment of episodic memory. Physical activity (total step count and step rate) was objectively assessed using an accelerometer, and hierarchical regressions were used to evaluate relationships between cognition and physical activity. Older adults performed more poorly on tasks of executive function and episodic memory. Physical activity was positively associated with a composite measure of visual episodic memory and face-name memory accuracy in older adults. Physical activity associations with cognition were independent of sedentary behavior, which was negatively correlated with memory performance. Physical activity was not associated with cognitive performance in younger adults. Physical activity is positively associated with episodic memory performance in aging. The relationship appears to be strongest for face-name relational memory and visual episodic memory, likely attributable to the fact that these tasks make strong demands on the hippocampus. The results suggest that physical activity relates to cognition in older, but not younger adults. PMID:26581790

  15. Active diffusion positions the nucleus in mouse oocytes.

    PubMed

    Almonacid, Maria; Ahmed, Wylie W; Bussonnier, Matthias; Mailly, Philippe; Betz, Timo; Voituriez, Raphaël; Gov, Nir S; Verlhac, Marie-Hélène

    2015-04-01

    In somatic cells, the position of the cell centroid is dictated by the centrosome. The centrosome is instrumental in nucleus positioning, the two structures being physically connected. Mouse oocytes have no centrosomes, yet harbour centrally located nuclei. We demonstrate how oocytes define their geometric centre in the absence of centrosomes. Using live imaging of oocytes, knockout for the formin 2 actin nucleator, with off-centred nuclei, together with optical trapping and modelling, we discover an unprecedented mode of nucleus positioning. We document how active diffusion of actin-coated vesicles, driven by myosin Vb, generates a pressure gradient and a propulsion force sufficient to move the oocyte nucleus. It promotes fluidization of the cytoplasm, contributing to nucleus directional movement towards the centre. Our results highlight the potential of active diffusion, a prominent source of intracellular transport, able to move large organelles such as nuclei, providing in vivo evidence of its biological function. PMID:25774831

  16. Draft position paper on knowledge management in space activities

    NASA Technical Reports Server (NTRS)

    Holm, Jeanne; Moura, Denis

    2003-01-01

    As other fields of industry, space activities are facing the challenge of Knowledge Management and the International Academy of Astronautics decided to settle in 2002 a Study Group to analyse the problem and issue general guidelines. This communication presents the draft position paper of this group in view to be discussed during the 2003 IAF Congress.

  17. Overcoming decommissioning challenges through client/laboratory co-operation

    SciTech Connect

    Wharton, Mike; Gray, Lesley

    2007-07-01

    Available in abstract form only. Full text of publication follows: Accelerated decommissioning projects of the type underway at the former gaseous diffusion plant at BNG Capenhurst, UK, involve characterisation and radiochemical fingerprinting of a variety of unusual materials derived from legacy wastes. The project management and technical challenges that can occur during such a program can be successfully surmounted if a close working relationship between the client and the analytical laboratory is achieved. The Capenhurst Integrated Decommissioning Program (IDP) is an example of how such co-operation can reduce costs and time scales by providing the analytical laboratory with key sample and technical information prior to the shipping of the samples to the lab. This ensures that challenges associated with unusual sample matrices can be anticipated and dealt with at an early stage in the project. Gamma spectrometry is the most common analytical technique when analysing samples for radioactive content as it is non-destructive, relatively inexpensive and fast. However, accurate measurement generally requires samples of a known density to be counted in calibrated geometries. This becomes a challenge as many legacy wastes comprise materials of uneven geometry and/or varying density, as has been the case during the Capenhurst IDP. Liaising with the client to ensure a representative sub-sample of the material is taken on-site, and a series of additional checks when analysing the sample ensure that accurate results are obtained even for non-routine materials. Often it is only one or two radionuclides that dominate the radioactive inventory for legacy wastes. (authors)

  18. Positioning.

    ERIC Educational Resources Information Center

    Conone, Ruth M.

    The key to positioning is the creation of a clear benefit image in the consumer's mind. One positioning strategy is creating in the prospect's mind a position that takes into consideration the company's or agency's strengths and weaknesses as well as those of its competitors. Another strategy is to gain entry into a position ladder owned by…

  19. Positive Active Material For Alkaline Electrolyte Storage Battert Nickel Electrodes

    DOEpatents

    Bernard, Patrick; Baudry, Michelle

    2000-12-05

    A method of manufacturing a positive active material for nickel electrodes of alkaline storage batteries which consists of particles of hydroxide containing mainly nickel and covered with a layer of a hydroxide phase based on nickel and yttrium is disclosed. The proportion of the hydroxide phase is in the range 0.15% to 3% by weight of yttrium expressed as yttrium hydroxide relative to the total weight of particles.

  20. 'Part of the solution': Developing sustainable energy through co-operatives and learning

    NASA Astrophysics Data System (ADS)

    Duguid, Fiona C. B.

    After five years of development, WindShare Co-operative in Toronto, Ontario became the first urban wind turbine in North America and the first co-operatively owned and operated wind turbine in Canada. The development of WindShare Co-operative has spurred the growth of a green energy co-operative sector in Ontario. This study, which included 27 interviews and a focus group with members of WindShare Co-operative, focuses on the roles of community-based green energy co-operatives in advancing sustainable energy development and energy literacy. Sustainable energy development is firmly rooted in the triple bottom line of environmental, social and economic success, and green energy co-operatives can be a way to help achieve those successes. Green energy co-operatives are structures for providing renewable energy generation or energy conservation practices, both of which have important environmental impacts regarding climate change and pollution levels. Co-operative structures are supported by processes that include local ownership, democracy, participation, community organizing, learning and social change. These processes have a significant social impact by creating a venue for people to be directly involved in the energy industry, by involving learning through participation in a community-based organization, and by advancing energy literacy within the membership and the general public. In regards to the economic impacts, green energy co-operatives foster a local economy and local investment opportunities, which have repercussions regarding building expertise within Ontario's green energy and co-operative development future, and more generally, captures members' interest because they have a direct stake in the co-operative. This thesis shows that green energy co-operatives, like WindShare, play an important role in advancing sustainable energy development, energy literacy and the triple bottom line. Members of WindShare expressed resounding feelings of pride, efficacy

  1. Surface Support Systems for Co-Operative and Integrated Human/Robotic Lunar Exploration

    NASA Technical Reports Server (NTRS)

    Mueller, Robert P.

    2006-01-01

    Human and robotic partnerships to realize space goals can enhance space missions and provide increases in human productivity while decreasing the hazards that the humans are exposed to. For lunar exploration, the harsh environment of the moon and the repetitive nature of the tasks involved with lunar outpost construction, maintenance and operation as well as production tasks associated with in-situ resource utilization, make it highly desirable to use robotic systems in co-operation with human activity. A human lunar outpost is functionally examined and concepts for selected human/robotic tasks are discussed in the context of a lunar outpost which will enable the presence of humans on the moon for extended periods of time.

  2. Active vibration control of a sandwich plate by non-collocated positive position feedback

    NASA Astrophysics Data System (ADS)

    Ferrari, Giovanni; Amabili, Marco

    2015-04-01

    The active vibration control of a free rectangular sandwich plate by using the Positive Position Feedback (PPF) algorithm was experimentally investigated in a previous study. Four normal modes were controlled by four nearly collocated couples of piezoelectric sensors and actuators. The experimental results of the control showed some limitation, especially in the Multi-Input Multi-Output (MIMO) configuration. This was attributed to the specific type of sensors and their conditioning, as well as to the phase shifts present in the vibration at different points of the structure. An alternative approach is here undertaken by abandoning the configuration of quasi-perfect collocation between sensor and actuator. The positioning of the piezoelectric patches is still led by the strain energy value distribution on the plate; each couple of sensor and actuator is now placed on the same face of the plate but in two distinct positions, opposed and symmetrical with respect to the geometric center of the plate. Single-Input Single-Output (SISO) PPF is tested and the transfer function parameters of the controller are tuned according to the measured values of modal damping. Then the participation matrices necessary for the MIMO control algorithm are determined by means of a completely experimental procedure. PPF is able to mitigate the vibration of the first four natural modes, in spite of the rigid body motions due to the free boundary conditions. The amplitude reduction achieved with the non-collocated configuration is much larger than the one obtained with the nearby collocated one. The phase lags were addressed in the MIMO algorithm by correction phase delays, further increasing the performance of the controller.

  3. Climate protection in Germany`s bilateral development co-operation with the People`s Republic of China

    SciTech Connect

    Schneider, A.

    1996-12-31

    For globally sustainable development to be achieved, three concerns are central: productive economic growth, social justice and ecological sustainability. Development co-operation supports the realisation of these three goals in partner countries by helping to alleviate poverty, promote economic growth through private-sector development and protect vital natural resources. The aim of globally sustainable development can only be achieved if industrial countries too implement necessary reforms and structural adjustments at every level. Co-operation efforts with partners must therefore be complemented by coherent policies at home. This is a matter of credibility, but also of developmental far-sightedness. Internal reforms in the industrial countries secure financial leeway for their providing foreign assistance in the longer term. Environmental and resource protection as a focal point of Germany`s development co-operation with the PRC aims to preserve vital natural resources, shape economic development in their partner countries in an ecologically sound manner and put China in a position to participate in global endeavours to protect the environment. Climate protection measures figure prominently in this area. This is justified given China`s share of global CO{sub 2} emissions and the potential for energy-saving measures and measures to increase power intensity. This potential is derived primarily from the possibility of using energy-efficient technologies, increasing the relatively low energy prices and making use of renewable sources of energy.

  4. The Effectiveness of Structured Co-Operative Teaching and Learning in Greek Primary School Classrooms

    ERIC Educational Resources Information Center

    Kaldi, Stavroula; Filippatou, Diamanto; Anthopoulou, Barbara

    2014-01-01

    This study focuses upon the effectiveness of structured co-operative group work on primary school students, aged between 8.5 and 9.5 years old, regarding their content knowledge, attitudes towards co-operative group work, experiential learning and open-ended curriculum as well as students' social and learning behaviour during co-operative…

  5. Co-Operative Education and the State, c.1895-1935

    ERIC Educational Resources Information Center

    Vernon, Keith

    2013-01-01

    The co-operative movement is currently exploring ways of engaging with changes in government education policy to develop schools with a distinctive co-operative ethos. While drawing on the opportunities in changing policy, these initiatives can also be seen as offering alternatives to the prevailing tenor of government thinking. This is not the…

  6. Co-Operative Problem-Solving at the Royal Docks Community School

    ERIC Educational Resources Information Center

    Martin, Ruth

    2013-01-01

    This article responds to Henry Tam's article in this issue of FORUM by exploring opportunities for co-operative problem-solving for staff and students of the Royal Docks Community School in the London Borough of Newham. Becoming a co-operative trust helped the school move out of special measures and develop a strategy of participation and…

  7. Ethics and Accountability: Participatory Research in a Worker Co-Operative.

    ERIC Educational Resources Information Center

    Mellor, Mary

    1988-01-01

    The author describes a participatory research project that took place in a garment workers' co-operative. The project's purpose was to record the history and working relationships of the co-operative in an attempt to help similar ventures. Problems of participatory research are considered. (CH)

  8. Dynamic positioning system based on active disturbance rejection technology

    NASA Astrophysics Data System (ADS)

    Lei, Zhengling; Guo, Chen; Fan, Yunsheng

    2015-08-01

    A dynamically positioned vessel, by the International Maritime Organization (IMO) and the certifying class societies (DNV, ABS, LR, etc.), is defined as a vessel that maintains its position and heading (fixed location or pre-determined track) exclusively by means of active thrusters. The development of control technology promotes the upgrading of dynamic positioning (DP) systems. Today there are two different DP systems solutions available on the market: DP system based on PID regulator and that based on model-based control. Both systems have limited disturbance rejection capability due to their design principle. In this paper, a new DP system solution is proposed based on Active Disturbance Rejection Control (ADRC) technology. This technology is composed of Tracking-Differentiator (TD), Extended State Observer (ESO) and Nonlinear Feedback Combination. On one hand, both TD and ESO can act as filters and can be used in place of conventional filters; on the other hand, the total disturbance of the system can be estimated and compensated by ESO, which therefore enhances the system's disturbance rejection capability. This technology's advantages over other methods lie in two aspects: 1) This method itself can not only achieve control objectives but also filter noisy measurements without other specialized filters; 2) This method offers a new useful approach to suppress the ocean disturbance. The simulation results demonstrate the effectiveness of the proposed method.

  9. Co-operation processes in dynamic environment management: evolution through training experienced pilots in flying a highly automated aircraft.

    PubMed

    Rogalski, J

    1996-01-01

    Dynamic environment management (process control, aircraft piloting, etc.) increasingly implies collective work components. Pragmatic purposes as well as epistemological interests raise important questions on collective activities at work. In particular, linked to the technological evolution in flight management, the role of the 'collective fact' appears as a key point in reliability. Beyond the development of individual competencies, the quality of the 'distributed' crew activity has to be questioned. This paper presents an empirical study about how experienced pilots co-ordinate their information and actions during the last period of training on a highly automated cockpit. A task of disturbance management (engine fire during takeoff) is chosen as amplifying cognitive requirements. Analysis focuses on the transitions between the main task and the incident to be managed. Crew performance and co-operation between two pilots are compared in three occurrences of the same task: the results are coherent with the hypothesis of a parallel evolution of the crew performance and its internal co-operation, and show that prescribed explicit co-operation is more present on action than on information about the 'state of the world'. Methodological issues are discussed about the possible effects of the specific situation of training, and about the psychological meaning of the results. PMID:11540153

  10. Global Positioning System Synchronized Active Light Autonomous Docking System

    NASA Technical Reports Server (NTRS)

    Howard, Richard T. (Inventor); Book, Michael L. (Inventor); Bryan, Thomas C. (Inventor); Bell, Joseph L. (Inventor)

    1996-01-01

    A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprising at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

  11. Global Positioning System Synchronized Active Light Autonomous Docking System

    NASA Technical Reports Server (NTRS)

    Howard, Richard (Inventor)

    1994-01-01

    A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprises at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

  12. The Distribution of Active Force Generators Controls Mitotic Spindle Position

    NASA Astrophysics Data System (ADS)

    Grill, Stephan W.; Howard, Jonathon; Schäffer, Erik; Stelzer, Ernst H. K.; Hyman, Anthony A.

    2003-07-01

    During unequal cell divisions a mitotic spindle is eccentrically positioned before cell cleavage. To determine the basis of the net force imbalance that causes spindle displacement in one-cell Caenorhabditis elegans embryos, we fragmented centrosomes with an ultraviolet laser. Analysis of the mean and variance of fragment speeds suggests that the force imbalance is due to a larger number of force generators pulling on astral microtubules of the posterior aster relative to the anterior aster. Moreover, activation of heterotrimeric guanine nucleotide-binding protein (G protein) α subunits is required to generate these astral forces.

  13. Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes.

    PubMed Central

    Emaduddin, M; Ekman, S; Rönnstrand, L; Heldin, C H

    1999-01-01

    To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor complexes of one kinase-active and one kinase-inactive receptor to mediate mitogenicity, chemotaxis and activation of mitogen-activated protein kinase revealed less efficient effects than those of heterodimers of wild-type receptors. Importantly, however, the fact that signalling capacities were retained illustrates a functional co-operation between the two receptor molecules in the dimer, where one receptor provides a functional kinase and the other acts as a substrate and provides docking sites for downstream signalling molecules. PMID:10417313

  14. Bidirectional associations between valued activities and adolescent positive adjustment in a longitudinal study: positive mood as a mediator.

    PubMed

    DesRoches, Andrea; Willoughby, Teena

    2014-02-01

    Although activity involvement has been linked to positive youth development, the value that adolescents place on these activities (i.e., how much they enjoy the activities, find them important, and spend time on them) has received less attention. The purpose of the present study was to examine the bidirectional longitudinal association between engagement in valued activities and adolescent positive adjustment (optimism, purpose in life, and self-esteem), as well as investigate a possible underlying mechanism for this link. High school students (N = 2,270, 48.7% female) from Ontario, Canada completed questionnaires annually in grades 10, 11, and 12. Auto-regressive cross-lagged path analyses were conducted over time, controlling for gender, parental education, and academic grades. Greater engagement in valued activities predicted higher optimism, purpose, and self-esteem over time. Importantly, the results did not support an alternate hypothesis of selection effects, in that adolescents who were better adjusted were not more likely than their peers to engage in valued activities over time. We also found that the longitudinal associations between valued activities and positive adjustment may be due partly to an underlying effect of increased positive mood. Thus, engagement in valued activities appears to be important for adolescent positive adjustment, and may help to foster thriving. Communities, educators, and parents should actively support and encourage adolescents to develop valued activities, and seek to ensure that there are ample opportunities and resources available for them to do so. PMID:23625185

  15. Activity of quinolones against gram-positive cocci: clinical features.

    PubMed

    Giamarellou, H

    1995-01-01

    The potential role of the commercially available fluoroquinolones in the treatment of Gram-positive infections is discussed on the basis of data obtained from animal experiments and clinical trials. In respiratory tract infections, and particularly in community-acquired pneumonia, it is evident that the presently available quinolones cannot be prescribed empirically as first-line therapy because of their borderline activity against Streptococcus pneumoniae and anaerobes. Reports of pneumococcal seeding in other tissues during quinolone therapy render their administration a debatable issue. Experience in endocarditis is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal osteomyelitis are included among cases of other bone infections. In noncontrolled studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal eradication rate ranging from 70 to 100%, while the addition of rifampicin has been proven to reduce the emergence of resistant mutants during therapy. In soft tissue and skin structure infections that also involve Gram-negative bacteria, ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci, respectively; however, the presence of diabetes or vascular disease compromised the success of treatment. In staphylococcal peritonitis complicating continuous ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or intraperitoneally were promising. In infections in neutropenic hosts, success of prophylaxis or therapy is still not clear, since colonisation and breakthrough bacteraemias with viridans streptococci and staphylococci have been reported. Furthermore, therapeutic results are compromised by the low response rate in Gram-positive infections. Despite the reported clinical efficacy of the newer fluoroquinolones, physicians should be alerted to the emergence of staphylococci resistant to fluoroquinolones

  16. UNESCO's Co-operation within the Framework of the Major Project for the Latin American and Caribbean Region: Reference Document PROMEDLAC V Meeting.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Santiago (Chile). Regional Office for Education in Latin America and the Caribbean.

    This report summarizes UNESCO's co-operation activities within the framework of the Major Project of Education in the field of Education in Latin America and the Caribbean between May 1991 and March 1993. Regional priorities had been established in Quito (Ecuador) in 1991 to focus on: (1) women as protagonists both in family life and economic…

  17. Conseil de la Cooperation Culturelle et Fonds Culturel. Rapport Annuel 1972. (Council for Cultural Co-operation and Cultural Fund. Annual Report 1972.)

    ERIC Educational Resources Information Center

    Council for Cultural Cooperation, Strasbourg (France).

    This document is a report on the activities of the Council for Cultural Co-Operation (CCC) and Cultural Fund for 1972. The CCC is briefly defined as being designed to reinforce educational and cultural cooperation among the 21 countries of the CCC, especially in matters of research, information, and documentation. The document is composed of…

  18. OECD (Organisation for Economic Co-Operation and Development): A Guide to Publications and Data Available in the Libraries of Duke University.

    ERIC Educational Resources Information Center

    Basefsky, Stuart, Comp.

    Designed to make Duke University's collection of OECD (Organisation for Economic Co-Operation and Development) publications and data more readily accessible, this guide is divided into the following sections: Introduction to OECD and Its Publications; General References about OECD and Its Activities; Indexes and Other Sources for Accessing OECD…

  19. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

    PubMed

    Carlsson, E; Ludvigsson, J; Huus, K; Faresjö, M

    2016-04-01

    Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity. PMID:25892449

  20. European tendencies and co-operation in the field of ITS systems - national achievements and challenges in Hungary

    NASA Astrophysics Data System (ADS)

    Lindenbach, Ágnes

    2016-06-01

    The article presents the role of intelligent transport systems/services related to the implementation of the essential European and Hungarian transport policy objectives. The `ITS Directive' will provide a framework for the tasks/works to be performed in the forthcoming years within the priority areas of ITS. The European Commission published regulations / specifications for the priority actions in the form of delegated acts defining the tasks/responsibilities of Member States. Regional/European co-operation for Hungary started after the EU-accession of the country. Hungary was an active partner within the European CONNECT and EasyWay projects, currently Hungary is a member of the CROCODILE consortium.

  1. South Asian co-operation in population programmes.

    PubMed

    Iqbal, M A

    1989-12-01

    Efforts by governments of South Asian countries to improve the economic growth and welfare of the people are being negated by high fertility. In some countries, the expenditures on health programs have increased and the programs have expanded rapidly without any concomitant improvement in efficiency or cost-effectiveness. This highlights the urgency of tackling the problems of not only population growth but also of managing population programs. There are similarities as well as differences in the management of population programs in the South Asian countries. Bangladesh has a population policy with a strong political will behind it. It also has a sound administrative structure and organization. Some areas that need attention are building up the operational relationship between health and family planning personnel, improved infrastructure development, more community involvement, and better evaluation. Some states in India have shown outstanding success in population programs, and some have successfully experimented with beyond family planning methods. A greater awareness of family planning among health staff, a solid information base for decision making, and management training for medical officers and staff are also needed. Pakistan's population program has had uneven results in the past, but it has now developed multi-sectoral components in decentralized field activities, involvement of local organizations and leaders, and better information, education, and social marketing, but it still needs to plan for evaluation and strengthen management training. Of the South Asian countries, Sri Lanka, with a high level of literacy and health care, has shown the best achievement in its social sector. The coverage through the maternal and child health service delivery system has been commendable with 94% of deliveries through institutions. Regional meetings have identified program management problem areas in 1) planning, control, and coordination of program implementation, 2

  2. Evolution of co-operation among mobile agents with different influence

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Chen, Tianyi; Wang, Xingpu; Jin, Jiuwu; Li, Mingchu

    2013-10-01

    Co-operation is a key factor in understanding the evolution of our society. Inspired by this issue, the individual mobility in game theory has been proved to be a very useful scenario. However, it is not realistic, as described in previous studies, that each agent has the same influence on its neighbour’s movement trait. In this work, we mainly focus on the weighted influence on the mobility of agents in the prisoner’s dilemma game. Here the weight is proportional to its degree with power exponent of λ, where λ is the adjustable parameter to control the level of heterogeneity among individuals in the network. Through numerous simulations we find that co-operation level is promoted when the heterogeneous influence factor is considered. In particular, there is an intermediate value λopt≈10 to guarantee the optimal evolution of co-operation. Moreover, we also prove that the effect of influence weight on the enhancement of co-operation is only valid when the agent’s interaction radius is within a threshold value. We thus present a viable method of understanding the ubiquitous co-operative behaviour in nature and hope that it will inspire further studies to resolve social dilemmas.

  3. Active Healthy Kids Canada's Position on Active Video Games for Children and Youth.

    PubMed

    Chaput, Jean-Philippe; Leblanc, Allana G; McFarlane, Allison; Colley, Rachel C; Thivel, David; Biddle, Stuart Jh; Maddison, Ralph; Leatherdale, Scott T; Tremblay, Mark S

    2013-12-01

    The effect of active video games (AVGs) on acute energy expenditure has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear. To address this knowledge gap, Active Healthy Kids Canada (AHKC) convened an international group of researchers to conduct a systematic review to understand whether AVGs should be promoted to increase physical activity and improve health indicators in children and youth (zero to 17 years of age). The present article outlines the process and outcomes of the development of the AHKC's position on active video games for children and youth. In light of the available evidence, AHKC does not recommend AVGs as a strategy to help children be more physically active. However, AVGs may exchange some sedentary time for light- to moderate-intensity physical activity, and there may be specific situations in which AVGs provide benefit (eg, motor skill development in special populations and rehabilitation). PMID:24497779

  4. Positional asphyxia without active restraint following an assault.

    PubMed

    Fernando, Tarini; Byard, Roger W

    2013-11-01

    Deaths due to positional asphyxia are most often accidental, associated with alcohol and/or drug intoxication. A 19-year-old male is reported who was assaulted and placed in a head-down position in the back of a car were he was later found dead. Brush abrasions indicated that he had been dragged to the vehicle. The head and right shoulder were wedged into the foot well with the body uppermost. At autopsy, there was marked congestion of the face, neck, and upper chest with conjunctival ecchymoses, bruising of the face and scalp, focal subarachnoid hemorrhage, minor cerebral contusion, and diffuse cerebral swelling with early hypoxic ischemic encephalopathy (HIE). Toxicology was negative. Death was attributed to HIE resulting from the unusual positioning of the body. Cases of positional asphyxia involving others may not always include restraint, and when encountered should initiate a careful evaluation of the possible events and lethal pathophysiological processes. PMID:23786332

  5. Novel co-operation between eotaxin and substance-P in inducing eosinophil-derived neurotoxin release.

    PubMed Central

    El-Shazly, A; Ishikawa, T

    1999-01-01

    Eosinophils, chemokines, and neuropeptides are thought to play effector roles in the pathogenesis of allergic diseases such as rhinitis. Eotaxin is a novel C-C chemokine with a potent and relatively specific eosinophil chemoattractant activity that binds selectively to CCR3 receptor, however, its activity in inducing eosinophil granules proteins release is poorly characterized. This study was performed to determine whether eotaxin primes eosinophil exocytosis and whether this co-operates with the sensory neuroimmune-axis. In the present communication, we show that 10 ng/ml eotaxin primed normal human eosinophil for exaggerated eosonophil-derived neurotoxin (EDN) release stimulated by 10(-8) M Substance-P (SP). This novel priming was blocked by; 7B11 and Herbimycin A (HA), the CCR3 antagonist and the tyrosine kinase inhibitor, respectively. SDS-Page studies showed significant tyrosine phosphorylation of several protein residues induced by 10(-8) M SP only after priming with 10 ng/ml eotaxin. These results demonstrate a novel co-operation between eotaxin and SP in inducing eosinophil cytotoxicity, which at least in part involves tyrosine kinases pathway(s). PMID:10704057

  6. Nuclear energy for peaceful uses: Status and salient issues for regional co-operation

    SciTech Connect

    Not Available

    1986-01-01

    Based on an expert group survey commissioned by ESCAP in preparation for the United Nations Conference for the Promotion of International Co-operation in the Peaceful Uses of Nuclear Energy, this report provides an overview of the current and potential uses of nuclear energy that could be harnessed by developing countries to support their development efforts. In particular, it highlights the agricultural, medical, and industrial applications of radioisotopes and radiation and underscores the need for regional and interregional co-operation in nuclear science and technology. Illustrated with charts, graphs, and tables.

  7. Active Women: Perspectives on Their Structural Position in the Community.

    ERIC Educational Resources Information Center

    Moyer, Harriett; And Others

    An exploratory pilot study to determine the personal characteristics of women community leaders and their position in the power structure was conducted in Chippewa and Eau Claire Counties, Wisconsin. The research design involved a comparison of three samples: the traditional power structure identified through reputational techniques; the active…

  8. Positive Youth Development through Physical Activity: Opportunities for Physical Educators

    ERIC Educational Resources Information Center

    Hemphill, Michael A.

    2014-01-01

    As physical educators continue to advocate for school-based PE, they should also consider ways to extend their work into community settings in an effort to ensure that all kids have an opportunity to develop physical literacy. This article describes how positive youth development programs can provide an opportunity for physical educators to engage…

  9. Collecting "Total" Vocational Education and Training Activity. Position Paper

    ERIC Educational Resources Information Center

    Karmel, Tom

    2011-01-01

    In this position paper, NCVER's Managing Director, Dr Tom Karmel, argues that the submission of vocational education and training student data should be mandated as a condition of registration for all registered training organisations, including private providers. This will ensure a comprehensive data collection that gives a realistic view of…

  10. Positive feedback of protein kinase C proteolytic activation during apoptosis.

    PubMed Central

    Leverrier, Sabrina; Vallentin, Alice; Joubert, Dominique

    2002-01-01

    In contrast with protein kinase Calpha (PKCalpha) and PKCepsilon, which are better known for promoting cell survival, PKCdelta is known for its pro-apoptotic function, which is exerted mainly through a caspase-3-dependent proteolytic activation pathway. In the present study, we used the rat GH3B6 pituitary adenoma cell line to show that PKCalpha and PKCepsilon are activated and relocalized together with PKCdelta when apoptosis is induced by a genotoxic stress. Proteolytic activation is a crucial step used by the three isoforms since: (1) the catalytic domains of the PKCalpha, PKCepsilon or PKCdelta isoforms (CDalpha, CDepsilon and CDdelta respectively) accumulated, and this accumulation was dependent on the activity of both calpain and caspase; and (2) transient expression of CDalpha, CDepsilon or CDdelta sufficed to induce apoptosis. However, following this initial step of proteolytic activation, the pathways diverge; cytochrome c release and caspase-3 activation are induced by CDepsilon and CDdelta, but not by CDalpha. Another interesting finding of the present study is the proteolysis of PKCdelta induced by CDepsilon expression that revealed the existence of a cross-talk between PKC isoforms during apoptosis. Hence the PKC family may participate in the apoptotic process of pituitary adenoma cells at two levels: downstream of caspase and calpain, and via retro-activation of caspase-3, resulting in the amplification of its own proteolytic activation. PMID:12238950

  11. Novel JAZ co-operativity and unexpected JA dynamics underpin Arabidopsis defence responses to Pseudomonas syringae infection.

    PubMed

    de Torres Zabala, Marta; Zhai, Bing; Jayaraman, Siddharth; Eleftheriadou, Garoufalia; Winsbury, Rebecca; Yang, Ron; Truman, William; Tang, Saijung; Smirnoff, Nicholas; Grant, Murray

    2016-02-01

    Pathogens target phytohormone signalling pathways to promote disease. Plants deploy salicylic acid (SA)-mediated defences against biotrophs. Pathogens antagonize SA immunity by activating jasmonate signalling, for example Pseudomonas syringae pv. tomato DC3000 produces coronatine (COR), a jasmonic acid (JA) mimic. This study found unexpected dynamics between SA, JA and COR and co-operation between JAZ jasmonate repressor proteins during DC3000 infection. We used a systems-based approach involving targeted hormone profiling, high-temporal-resolution micro-array analysis, reverse genetics and mRNA-seq. Unexpectedly, foliar JA did not accumulate until late in the infection process and was higher in leaves challenged with COR-deficient P. syringae or in the more resistant JA receptor mutant coi1. JAZ regulation was complex and COR alone was insufficient to sustainably induce JAZs. JAZs contribute to early basal and subsequent secondary plant defence responses. We showed that JAZ5 and JAZ10 specifically co-operate to restrict COR cytotoxicity and pathogen growth through a complex transcriptional reprogramming that does not involve the basic helix-loop-helix transcription factors MYC2 and related MYC3 and MYC4 previously shown to restrict pathogen growth. mRNA-seq predicts compromised SA signalling in a jaz5/10 mutant and rapid suppression of JA-related components on bacterial infection. PMID:26428397

  12. The Tyranny of No Alternative: Co-Operating in a Competitive Marketplace

    ERIC Educational Resources Information Center

    Mills, Martin

    2015-01-01

    This paper explores the decisions made by one secondary school in a major English city to become a co-operative academy. This school is located in an area affected by economic hardship and social and cultural tensions. The school, prior to its conversion to an academy, was well known in the local area for its commitment to social justice…

  13. The Case of the Missing Organizations: Co-operatives and the Textbooks.

    ERIC Educational Resources Information Center

    Hill, Roderick

    2000-01-01

    States that co-operative (co-op) economics organizations are ignored in economic introductory textbooks in North America and provides evidence for this assertion. Addresses how to deal with this form of economic organization. Argues that asking who makes the decisions in firms and why, using co-ops as an example, raises important questions. (CMK)

  14. Missing--The People's Voice: Organisation for Economic Co-Operation and Development

    ERIC Educational Resources Information Center

    Pike, Patricia

    2014-01-01

    Sustainable development in education for future economic growth has always been a global focal point for non-governmental agencies across the world. This article highlights the extensive work the Organisation for Economic Co-operation Development (OECD) has achieved over time, constructing contemporary society as we know it today, continually…

  15. Effects of a Co-operative Learning Strategy on Ninth-Graders' Understanding of Human Nutrition.

    ERIC Educational Resources Information Center

    Soyibo, Kola; Evans, Hermel G.

    2002-01-01

    Looks at the effect of teaching strategies on a group's attitude toward biology and understanding human nutrition. Used an experimental group that participated in co-operative learning and a control group taught using the lecture method. Involves ninth graders (n=156) from two high schools in Jamaica. (Author/YDS)

  16. From competition to co-operation: new economic relationships in the National Health Service.

    PubMed

    Goddard, M; Mannion, R

    1998-03-01

    The Labour government has outlined its plans to 'replace' the competitive internal market with a more collaborative system based on partnership. Agreement amongst purchasers and providers is to be based on co-operation rather than competition. Longer term agreements covering periods of 3-5 years are to replace annual contracts within this new environment. The aim of this paper is to explore the potential economic implications of these policy changes by drawing on the economics of co-operation and the transaction costs approach to longer term contracting. Issues surrounding the role of trust in contractual relationships are explored and the relevance of experience and evidence from non-health care sectors is considered in the context of the NHS. It is concluded that both theory and empirical evidence suggest that co-operation and trust can play a central role in the efficient organisation of contractual arrangements in circumstances similar to those under which the NHS operates. However, we warn against the expectation that the policy changes will produce automatically the scale of benefits predicted by the Labour government, especially as they will have to find a way of extracting reasonable performance from providers under a system of collaboration and long term agreements. They may find they need to tread a fine line between competition and co-operation in order to reap the benefits of both. PMID:9565167

  17. Environmental Engineering Education (E3) in the Gulf Co-Operation Countries

    ERIC Educational Resources Information Center

    Jassim, Majeed; Coskuner, Gulnur

    2007-01-01

    The six members of the Gulf Co-operation Countries (GCC)--Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates--are facing enormous environmental challenges associated with rapid urbanisation and industrialisation, especially in the last three decades, due to its role as a global hydrocarbon energy centre. None of these…

  18. Organized network for supporting the amateur-scientist co-operation in Finland

    NASA Astrophysics Data System (ADS)

    Mäkelä, V.; Haukka, H.; Oksanen, A.; Hentunen, V.-P.

    2014-04-01

    PROAM network is a working group of Ursa Astronomical Association [1] for supporting Finnish amateur astronomers participating to co-operation projects between professional and amateur astronomers. The network relays the information on projects, maintains professional contacts and arranges training on technical skills for research work.

  19. Learner Oriented Co-Operative Learning: A Booster to Higher Educational Learners

    ERIC Educational Resources Information Center

    Singaravelu, G.

    2007-01-01

    The present study enlightens the impact of Learner-Oriented-Co-operative Learning in enriching knowledge in Environmental Education at Higher Education. To achieve the expected competency in Biodiversity, various approaches were adopted in the class room transaction which were not fruitful. Hence the researcher practiced the Learner-Oriented-Co…

  20. International Co-Operation in Control Engineering Education Using Online Experiments

    ERIC Educational Resources Information Center

    Henry, Jim; Schaedel, Herbert M.

    2005-01-01

    This paper describes the international co-operation experience in teaching control engineering with laboratories being conducted remotely by students via the Internet. This paper describes how the students ran the experiments and their personal experiences with the laboratory. A tool for process identification and controller tuning based on…

  1. Using Peer Teaching to Support Co-Operative Learning in Undergraduate Pharmacology

    ERIC Educational Resources Information Center

    Depaz, Iris; Moni, Roger W.

    2008-01-01

    We report findings from the second phase of a study of co-operative, group-based assessment in Pharmacology for second-year undergraduates at The University of Queensland, Australia. Students (n = 285) enrolled in the 2006 Bachelor of Science degree program completed a group-based assessment task (weighted 10% of their course). Blended teaching…

  2. Gestalt Revisited: Spin-Offs and Assessment in International University Co-Operation

    ERIC Educational Resources Information Center

    Denman, Brian D.

    2004-01-01

    International university co-operation is in a constant state of metamorphosis. Its future rests upon extraneous forces such as globalization and internationalization and also upon those who make policy decisions. Many international university organizations are auditing their programs and initiatives to such a degree that the cost effectiveness of…

  3. Position paper on active countermeasures for computer networks.

    SciTech Connect

    Van Randwyk, Jamie A.

    2003-07-01

    Computer security professionals have used passive network countermeasures for several years in order to secure computer networks. Passive countermeasures such as firewalls and intrusion detection systems are effective but their use alone is not enough to protect a network. Active countermeasures offer new ways of protecting a computer network. Corporations and government entities should adopt active network countermeasures as a means of protecting their computer networks.

  4. GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii

    PubMed Central

    Costa, Frederico R. C.; Mota, Caroline M.; Santiago, Fernanda M.; Silva, Murilo V.; Ferreira, Marcela D.; Fonseca, Denise M.; Silva, João S.; Mineo, José R.; Mineo, Tiago W. P.

    2016-01-01

    Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection. PMID:27027302

  5. Real-Time GNSS Positioning Along Canada's Active Coastal Margin

    NASA Astrophysics Data System (ADS)

    Henton, J. A.; Dragert, H.; Lu, Y.

    2014-12-01

    High-rate, low-latency Global Navigation Satellite System (GNSS) data are being refined for real-time applications to monitor and report motions related to large earthquakes in coastal British Columbia. Given the tectonic setting of Canada's west coast, specific goals for real-time regional geodetic monitoring are: (1) the collection of GNSS data with adequate station density to identify the deformation field for regional earthquakes with M>7.3; (2) the robust, continuous real-time analyses of GNSS data with a precision of 1-2 cm and a latency of less than 10s; and (3) the display of results with attending automated alarms and estimations of earthquake parameters. Megathrust earthquakes (M>8) are the primary targets for immediate identification, since the tsunamis they generate will strike the coast within 15 to 20 min. However, large (6.0positioning streams for regional sites received from the Canadian Geodetic Survey (CGS), the Jet Propulsion Laboratory (JPL), and the Plate Boundary Observatory (PBO). The comparison of these various real-time solutions allows a realistic evaluation of day-to-day software performance especially when faced with adverse conditions such as data gaps or poor satellite geometry. Forward models for scenario earthquakes in this region are used to "fingerprint" the coseismic displacements expected from various offshore events which allows an evaluation of the effectiveness of the current regional coverage. The present distribution and density of real-time sites is largely sufficient for aiding the timely estimation of size, location

  6. Novel positive allosteric modulators of GABAA receptors with anesthetic activity

    PubMed Central

    Maldifassi, Maria C.; Baur, Roland; Pierce, David; Nourmahnad, Anahita; Forman, Stuart A.; Sigel, Erwin

    2016-01-01

    GABAA receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics and anesthetics. We previously identified novel ligands of the classical benzodiazepine binding pocket in α1β2γ2 GABAA receptors using an experiment-guided virtual screening (EGVS) method. This screen also identified novel ligands for intramembrane low affinity diazepam site(s). In the current study we have further characterized compounds 31 and 132 identified with EGVS as well as 4-O-methylhonokiol. We investigated the site of action of these compounds in α1β2γ2 GABAA receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology combined with a benzodiazepine site antagonist and transmembrane domain mutations. All three compounds act mainly through the two β+/α− subunit transmembrane interfaces of the GABAA receptors. We then used concatenated receptors to dissect the involvement of individual β+/α− interfaces. We further demonstrated that these compounds have anesthetic activity in a small aquatic animal model, Xenopus laevis tadpoles. The newly identified compounds may serve as scaffolds for the development of novel anesthetics. PMID:27198062

  7. Co-operative interactions between NFAT (nuclear factor of activated T cells) c1 and the zinc finger transcription factors Sp1/Sp3 and Egr-1 regulate MT1-MMP (membrane type 1 matrix metalloproteinase) transcription by glomerular mesangial cells.

    PubMed Central

    Alfonso-Jaume, Maria Alejandra; Mahimkar, Rajeev; Lovett, David H

    2004-01-01

    The transition of normally quiescent glomerular MCs (mesangial cells) to a highly proliferative phenotype with characteristics of myofibroblasts is a process commonly observed in inflammatory diseases affecting the renal glomerulus, the ultimate result of which is glomerulosclerosis. Generation of proteolytically active MMP (matrix metalloproteinase)-2 by the membrane-associated membrane type 1 (MT1)-MMP is responsible for the transition of mesangial cells to the myofibroblast phenotype [Turck, Pollock, Lee, Marti and Lovett (1996) J. Biol. Chem. 271, 15074-15083]. In the present study, we show that the expression of MT1-MMP within the context of MCs is mediated by three discrete cis -acting elements: a proximal non-canonical Sp1 site that preferentially binds Sp1; an overlapping Sp1/Egr-1-binding site that preferentially binds Egr-1; and a more distal binding site for the NFAT (nuclear factor of activated T cells) that binds the NFAT c1 isoform present in MC nuclear extracts. Transfection with an NFAT c1 expression plasmid, or activation of calcineurin with a calcium ionophore, yielded major increases in NFAT c1 nuclear DNA-binding activity, MT1-MMP transcription and protein synthesis, which were additive with the lower levels of transactivation provided by the proximal Sp1 and the overlapping Sp1/Egr-1 sites. Specific binding of NFAT c1 to the MT1-MMP promoter was confirmed by chromatin immunoprecipitation studies, while MT1-MMP expression was suppressed by treatment with the calcineurin inhibitor, cyclosporin A. These studies are the first demonstration that a specific NFAT isoform enhances transcription of an MMP (MT1-MMP) that plays a major role in the proteolytic events that are a dominant feature of acute glomerular inflammation. Suppression of MT1-MMP by commonly used calcineurin inhibitors may play a role in the development of renal fibrosis following renal transplantation. PMID:14979875

  8. Brain activations during judgments of positive self-conscious emotion and positive basic emotion: pride and joy.

    PubMed

    Takahashi, Hidehiko; Matsuura, Masato; Koeda, Michihiko; Yahata, Noriaki; Suhara, Tetsuya; Kato, Motoichiro; Okubo, Yoshiro

    2008-04-01

    We aimed to investigate the neural correlates associated with judgments of a positive self-conscious emotion, pride, and elucidate the difference between pride and a basic positive emotion, joy, at the neural basis level using functional magnetic resonance imaging. Study of the neural basis associated with pride might contribute to a better understanding of the pride-related behaviors observed in neuropsychiatric disorders. Sixteen healthy volunteers were studied. The participants read sentences expressing joy or pride contents during the scans. Pride conditions activated the right posterior superior temporal sulcus and left temporal pole, the regions implicated in the neural substrate of social cognition or theory of mind. However, against our prediction, we did not find brain activation in the medial prefrontal cortex, a region responsible for inferring others' intention or self-reflection. Joy condition produced activations in the ventral striatum and insula/operculum, the key nodes of processing of hedonic or appetitive stimuli. Our results support the idea that pride is a self-conscious emotion, requiring the ability to detect the intention of others. At the same time, judgment of pride might require less self-reflection compared with those of negative self-conscious emotions such as guilt or embarrassment. PMID:17638925

  9. Effect of seat positions on discomfort, muscle activation, pressure distribution and pedal force during cycling.

    PubMed

    Verma, Rachita; Hansen, Ernst A; de Zee, Mark; Madeleine, Pascal

    2016-04-01

    The aim of this study was to measure and analyse discomfort and biomechanics of cycling, i.e., muscle activation, centre of pressure of seat pressure profiles and pedal forces as a function of seat position. Twenty-one recreationally active individuals cycled for 10min at 100W on an ergometer cycle using five different seat positions. The neutral position was considered as basic seat position and was compared with upward, downward, forward and backward seat positions. The initial bout was repeated at the end of the recording session. Discomfort increased for upward and backward condition compared with neutral (P<0.05). Normalized surface electromyography from gastrocnemius decreased in the downward and forward position but increased in the upward and backward position. The minimum force became less negative for forward position compared with neutral seat position (P<0.05). The degree of variability of centre of pressure increased in the upward and backward position and the entropy of the centre of pressure of sitting posture for backward position decreased compared with neutral seat position (P<0.05). The present study revealed that consecutive changes of seat position over time lead to increase in discomfort as well as alterations of the biomechanics of cycling. PMID:26938676

  10. Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate

    PubMed Central

    Hughes, Michelle A.; Powley, Ian R.; Jukes-Jones, Rebekah; Horn, Sebastian; Feoktistova, Maria; Fairall, Louise; Schwabe, John W.R.; Leverkus, Martin; Cain, Kelvin; MacFarlane, Marion

    2016-01-01

    Summary The death-inducing signaling complex (DISC) initiates death receptor-induced apoptosis. DISC assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL only) or anti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation. Current models assume that c-FLIP directly competes with procaspase-8 for recruitment to FADD. Using a functional reconstituted DISC, structure-guided mutagenesis, and quantitative LC-MS/MS, we show that c-FLIPL/S binding to the DISC is instead a co-operative procaspase-8-dependent process. FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes with c-FLIPL/S via a hierarchical binding mechanism. Procaspase-8 activation is regulated by the ratio of unbound c-FLIPL/S to procaspase-8, which determines composition of the procaspase-8:c-FLIPL/S heterodimer. Thus, procaspase-8:c-FLIPL exhibits localized enzymatic activity and is preferentially an activator, promoting DED-mediated procaspase-8 oligomer assembly, whereas procaspase-8:c-FLIPS lacks activity and potently blocks procaspase-8 activation. This co-operative hierarchical binding model explains the dual role of c-FLIPL and crucially defines how c-FLIP isoforms differentially control cell fate. PMID:26990987

  11. Positive affect modulates activity in the visual cortex to images of high calorie foods.

    PubMed

    Killgore, William D S; Yurgelun-Todd, Deborah A

    2007-05-01

    Activity within the visual cortex can be influenced by the emotional salience of a stimulus, but it is not clear whether such cortical activity is modulated by the affective status of the individual. This study used functional magnetic resonance imaging (fMRI) to examine the relationship between affect ratings on the Positive and Negative Affect Schedule and activity within the occipital cortex of 13 normal-weight women while viewing images of high calorie and low calorie foods. Regression analyses revealed that when participants viewed high calorie foods, Positive Affect correlated significantly with activity within the lingual gyrus and calcarine cortex, whereas Negative Affect was unrelated to visual cortex activity. In contrast, during presentations of low calorie foods, affect ratings, regardless of valence, were unrelated to occipital cortex activity. These findings suggest a mechanism whereby positive affective state may affect the early stages of sensory processing, possibly influencing subsequent perceptual experience of a stimulus. PMID:17464782

  12. Safety management in multiemployer worksites in the manufacturing industry: opinions on co-operation and problems encountered.

    PubMed

    Nenonen, Sanna; Vasara, Juha

    2013-01-01

    Co-operation between different parties and effective safety management play an important role in ensuring safety in multiemployer worksites. This article reviews safety co-operation and factors complicating safety management in Finnish multiemployer manufacturing worksites. The paper focuses on the service providers' opinions; however, a comparison of the customers' views is also presented. The results show that safety-related co-operation between providers and customers is generally considered as successful but strongly dependent on the partner. Safety co-operation is provided through, e.g., training, orientation and risk analysis. Problems encountered include ensuring adequate communication, identifying hazards, co-ordinating work tasks and determining responsibilities. The providers and the customers encounter similar safety management problems. The results presented in this article can help companies to focus their efforts on the most problematic points of safety management and to avoid common pitfalls. PMID:23759189

  13. Educational Co-operation in Asia and the Pacific: 30 Years of NIER's Activities.

    ERIC Educational Resources Information Center

    Watanabe, Ryo, Ed.; Numano, Taro, Ed.; Nagata, Yoshiyuki, Ed.

    The history of the regional cooperation program of the National Institute for Educational Research (NIER) is recorded in this document. Specifically, the report outlines the past 30 years of the program in Asia and the Pacific. Throughout those years, 93 seminars, workshops, and symposia have been organized. In addition, information about the…

  14. Excerpts from "Position Statement on Physical Fitness and Activity in the Context of Leisure Education."

    ERIC Educational Resources Information Center

    Ruskin, Hilleil

    2002-01-01

    Presents a position statement designed to inform governments, non-governmental organizations, and education institutions about the significance and benefits of physical activity for all and establish a clear relationship between physical activity and leisure education. The statement includes specific recommendations for leisure education and…

  15. Positive Behavior Interventions and Support in a Physical Activity Summer Camp

    ERIC Educational Resources Information Center

    Hinton, Vanessa; Buchanan, Alice M.

    2015-01-01

    This purpose of this study was to investigate the implementation of positive behavior interventions and support (PBIS) in a summer camp. The camp provided physical activity opportunities to underserved children attending a summer program at a local, rural public school. Certified physical education teachers led activity stations. Participants in…

  16. Physical Activity and Psychological Benefits. International Society of Sport Psychology Position Statement.

    ERIC Educational Resources Information Center

    Physician and Sportsmedicine, 1992

    1992-01-01

    International Society of Sport Psychology clarifies the psychological benefits of physical activity, noting the positive relationship between physical activity level and mental health. Exercise can reduce anxiety, decrease depression levels, reduce neuroticism and anxiety, reduce stress, and have beneficial emotional effects for both sexes across…

  17. Alignment of Hands-On STEM Engagement Activities with Positive STEM Dispositions in Secondary School Students

    ERIC Educational Resources Information Center

    Christensen, Rhonda; Knezek, Gerald; Tyler-Wood, Tandra

    2015-01-01

    This study examines positive dispositions reported by middle school and high school students participating in programs that feature STEM-related activities. Middle school students participating in school-to-home hands-on energy monitoring activities are compared to middle school and high school students in a different project taking part in…

  18. Adaptability and Prediction of Anticipatory Muscular Activity Parameters to Different Movements in the Sitting Position.

    PubMed

    Chikh, Soufien; Watelain, Eric; Faupin, Arnaud; Pinti, Antonio; Jarraya, Mohamed; Garnier, Cyril

    2016-08-01

    Voluntary movement often causes postural perturbation that requires an anticipatory postural adjustment to minimize perturbation and increase the efficiency and coordination during execution. This systematic review focuses specifically on the relationship between the parameters of anticipatory muscular activities and movement finality in sitting position among adults, to study the adaptability and predictability of anticipatory muscular activities parameters to different movements and conditions in sitting position in adults. A systematic literature search was performed using PubMed, Science Direct, Web of Science, Springer-Link, Engineering Village, and EbscoHost. Inclusion and exclusion criteria were applied to retain the most rigorous and specific studies, yielding 76 articles, Seventeen articles were excluded at first reading, and after the application of inclusion and exclusion criteria, 23 were retained. In a sitting position, central nervous system activity precedes movement by diverse anticipatory muscular activities and shows the ability to adapt anticipatory muscular activity parameters to the movement direction, postural stability, or charge weight. In addition, these parameters could be adapted to the speed of execution, as found for the standing position. Parameters of anticipatory muscular activities (duration, order, and amplitude of muscle contractions constituting the anticipatory muscular activity) could be used as a predictive indicator of forthcoming movement. In addition, this systematic review may improve methodology in empirical studies and assistive technology for people with disabilities. PMID:27440765

  19. Co-Operation and Co-Funding Networks in eHealth Research.

    PubMed

    Kokol, Peter; Blažun Vošner, Helena; Saranto, Kaija

    2016-01-01

    In our bibliometric study we were interested in development and global trends in information and communication technology resulted in the emergence of cooperation and co-funding networks in eHealth research. The corpus was formed from the Web of Science Core Collection using the search keyword string "eHealth" in information source titles, abstracts, and keywords for the time period 2005-2014. The study results show that the research in eHealth is globally dispersed, however most co-operation is performed on the local continent or country level. Most co-founding is done among pharmaceutical firms themselves, however Sanofi, Merck and Abbot also co-fund the same projects as funding agencies. PMID:27332426

  20. A second international co-operative investigation into thioacetazone side-effects*

    PubMed Central

    Miller, A. B.; Nunn, A. J.; Robinson, D. K.; Ferguson, G. C.; Fox, Wallace; Tall, Ruth

    1970-01-01

    As part of a large-scale international, co-operative investigation into the side-effects produced by thioacetazone employed in the treatment of tuberculosis, an evaluation has been made of a supplement incorporating vitamins and an antihistamine as a prophylactic. Over a 12-week period of treatment, the additive supplement failed to reduce the over-all frequency of side-effects or the frequency of side-effects leading to a major departure from prescribed treatment. There was also no evidence that the more serious side-effects, particularly rashes, jaundice and agranulocytosis, were reduced by the additives, although the occurrence of vomiting, which was however infrequent, was reduced. In view of this lack of appreciable benefit, as well as the higher cost and impaired keeping properties of tablets containing thioacetazone plus isoniazid when the supplement is added, the use of the supplement as a prophylactic cannot be recommended. PMID:4098113

  1. Alignment of Hands-on STEM Engagement Activities with Positive STEM Dispositions in Secondary School Students

    NASA Astrophysics Data System (ADS)

    Christensen, Rhonda; Knezek, Gerald; Tyler-Wood, Tandra

    2015-12-01

    This study examines positive dispositions reported by middle school and high school students participating in programs that feature STEM-related activities. Middle school students participating in school-to-home hands-on energy monitoring activities are compared to middle school and high school students in a different project taking part in activities such as an after-school robotics program. Both groups are compared and contrasted with a third group of high school students admitted at the eleventh grade to an academy of mathematics and science. All students were assessed using the same science, technology, engineering and mathematics (STEM) dispositions instrument. Findings indicate that the after-school group whose participants self-selected STEM engagement activities, and the self-selected academy of mathematics and science group, each had highly positive STEM dispositions comparable to those of STEM professionals, while a subset of the middle school whole-classroom energy monitoring group that reported high interest in STEM as a career, also possessed highly positive STEM dispositions comparable to the STEM Professionals group. The authors conclude that several different kinds of hands-on STEM engagement activities are likely to foster or maintain positive STEM dispositions at the middle school and high school levels, and that these highly positive levels of dispositions can be viewed as a target toward which projects seeking to interest mainstream secondary students in STEM majors in college and STEM careers, can hope to aspire. Gender findings regarding STEM dispositions are also reported for these groups.

  2. Loss of Rassf1a co-operates with ApcMin to accelerate intestinal tumourigenesis

    PubMed Central

    van der Weyden, L.; Arends, M.J.; Dovey, O.M.; Harrison, H. L.; Lefebvre, G.; Conte, N.; Gergely, F.V.; Bradley, A.; Adams, D.J.

    2013-01-01

    Promoter methylation of the RAS-association domain family 1, isoform A gene (RASSF1A) is one of the most frequent events found in human tumours. In this study we set out to test the hypothesis that loss of Rassf1a can co-operate with inactivation of the adenomatous polyposis coli (Apc) gene to accelerate intestinal tumourigenesis using the Apc-Min (ApcMin/+) mouse model, as mutational or deletional inactivation of APC is a frequent early event in the genesis of intestinal cancer. Further, loss of RASSF1A has also been reported to occur in premalignant adenomas of the bowel. RASSF1A has been implicated in an array of pivotal cellular processes, including regulation of the cell cycle, apoptosis, microtubule stability and most recently in the β-catenin signalling pathway. By interbreeding isoform specific Rassf1a knockout mice with Apc+/Min mice we showed that loss of Rassf1a results in a significant increase in adenomas of the small intestine and accelerated intestinal tumourigenesis leading to the earlier death of adenocarcinoma-bearing mice and decreased overall survival. Comparative genomic hybridization of adenomas from Rassf1a−/−; Apc+/Min mice revealed no evidence of aneuploidy or gross chromosomal instability (no difference to adenomas from Rassf1a+/+; Apc+/Min mice). Immunohistochemical analysis of adenomas revealed increased nuclear β-catenin accumulation in adenomas from Rassf1a−/−; Apc+/Min mice, compared to those from Rassf1a+/+; Apc+/Min mice, but no differences in proliferation marker (Ki67) staining patterns. Collectively these data demonstrate co-operation between inactivation of Rassf1a and Apc resulting in accelerated intestinal tumourigenesis, with adenomas showing increased nuclear accumulation of β-catenin, supporting a mechanistic link via loss of the known interaction of Rassf1 with β-TrCP that usually mediates degradation of β-catenin. PMID:18391979

  3. Site selection and characterization for historic low-level radioactive wastes in Ontario, Co-operative Siting Process

    SciTech Connect

    Paktunc, A.D.

    1993-12-31

    The Co-operative Siting Process is a non-confrontational way to site a low-level radioactive waste (LLRW) management facility in Ontario. The facility will be designed to accommodate approximately 880,000 m{sup 3} of LLRW. Four sets of general facility concepts, appropriate for the physical and chemical characteristics of the wastes and the general site conditions, are being considered. These include engineered mounds, shallow burial in trenches, burial in open pit with previous surround, and intermediate depth rock disposal concepts. The communities interested in offering a site are located in the Canadian Shield where the topography is dominated by rolling hills with reliefs of up to 50 meters and hydrogeological conditions are primarily controlled by fractures in the rock and by the types and distribution of glacial sediments. Climatic conditions can be classified as humid-continental. The objective of site characterization activity is to assess the suitability of potential sites for long-term containment of LLRW in the geosphere and their safe isolation from the biosphere. An initial phase involves exploratory studies designed to reduce larger areas to smaller areas and eventually to candidate sites. The second phase involves site-specific studies designed to maximize the changes of identifying more than one site for different facility requirements and complying with the regulatory requirements and performance expectations.

  4. Directed evolution of Tau class glutathione transferases reveals a site that regulates catalytic efficiency and masks co-operativity.

    PubMed

    Axarli, Irine; Muleta, Abdi W; Vlachakis, Dimitrios; Kossida, Sophia; Kotzia, Georgia; Maltezos, Anastasios; Dhavala, Prathusha; Papageorgiou, Anastassios C; Labrou, Nikolaos E

    2016-03-01

    A library of Tau class GSTs (glutathione transferases) was constructed by DNA shuffling using the DNA encoding the Glycine max GSTs GmGSTU2-2, GmGSTU4-4 and GmGSTU10-10. The parental GSTs are >88% identical at the sequence level; however, their specificity varies towards different substrates. The DNA library contained chimaeric structures of alternated segments of the parental sequences and point mutations. Chimaeric GST sequences were expressed in Escherichia coli and their enzymatic activities towards CDNB (1-chloro-2,4-dinitrobenzene) and the herbicide fluorodifen (4-nitrophenyl α,α,α-trifluoro-2-nitro-p-tolyl ether) were determined. A chimaeric clone (Sh14) with enhanced CDNB- and fluorodifen-detoxifying activities, and unusual co-operative kinetics towards CDNB and fluorodifen, but not towards GSH, was identified. The structure of Sh14 was determined at 1.75 Å (1 Å=0.1 nm) resolution in complex with S-(p-nitrobenzyl)-glutathione. Analysis of the Sh14 structure showed that a W114C point mutation is responsible for the altered kinetic properties. This was confirmed by the kinetic properties of the Sh14 C114W mutant. It is suggested that the replacement of the bulky tryptophan residue by a smaller amino acid (cysteine) results in conformational changes of the active-site cavity, leading to enhanced catalytic activity of Sh14. Moreover, the structural changes allow the strengthening of the two salt bridges between Glu(66) and Lys(104) at the dimer interface that triggers an allosteric effect and the communication between the hydrophobic sites. PMID:26637269

  5. Greater positive schizotypy relates to reduced N100 activity during rejection scenes.

    PubMed

    Premkumar, Preethi; Onwumere, Juliana; Wilson, Daniel; Sumich, Alexander; Castro, Antonio; Kumari, Veena; Kuipers, Elizabeth

    2014-08-01

    Social anxiety due to rejection sensitivity (RS) exacerbates psychosis-like experiences in the general population. While reduced dorsal anterior cingulate cortex (dACC) activity during social rejection in high schizotypy has suggested self-distancing from rejection, earlier stages of mental processing such as feature encoding could also contribute to psychosis-like experiences. This study aimed to determine the stage of mental processing of social rejection that relates to positive schizotypy. Forty-one healthy participants were assessed for schizotypy and RS. Event-related potential amplitudes (ERPs) were measured at frontal, temporal and parieto-occipital sites and their cortical sources (dACC, temporal pole and lingual gyrus) at early (N100) and late (P300 and late slow wave, LSW) timeframes during rejection, acceptance and neutral scenes. ERPs were compared between social interaction types. Correlations were performed between positive schizotypy (defined as the presence of perceptual aberrations, hallucinatory experiences and magical thinking), RS and ERPs during rejection. Amplitude was greater during rejection than acceptance or neutral conditions at the dACC-P300, parieto-occipital-P300, dACC-LSW and frontal-LSW. RS correlated positively with positive schizotypy. Reduced dACC N100 activity during rejection correlated with greater positive schizotypy and RS. Reduced dACC N100 activity and greater RS independently predicted positive schizotypy. An N100 deficit that indicates reduced feature encoding of rejection scenes increases with greater positive schizotypy and RS. Higher RS shows that a greater tendency to misattribute ambiguous social situations as rejecting also increases with positive schizotypy. These two processes, namely primary bottom-up sensory processing and secondary misattribution of rejection, combine to increase psychosis-like experiences. PMID:25010933

  6. p21-activated kinase 4 regulates mitotic spindle positioning and orientation.

    PubMed

    Bompard, Guillaume; Morin, Nathalie

    2012-01-01

    During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex. Spindle orientation is also regulated by integrin-mediated cell adhesion and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell. Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis. In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial. Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division. In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation. PMID:22960742

  7. HIV Serosorting, Status Disclosure, and Strategic Positioning Among Highly Sexually Active Gay and Bisexual Men.

    PubMed

    Grov, Christian; Rendina, H Jonathon; Moody, Raymond L; Ventuneac, Ana; Parsons, Jeffrey T

    2015-10-01

    Researchers have identified harm reduction strategies that gay, bisexual, and other men who have sex with men (GBMSM) use to reduce HIV transmission--including serosorting, status disclosure, and strategic positioning. We report on patterns of these behaviors among 376 highly sexually active (i.e., 9+partners, <90 days) GBMSM: mean age of 37, 49.5% men of color, 87.8% gay identified, 57.5% college educated. We found evidence that many men engaged in serosorting, status disclosure, and strategic positioning; however, rates varied based on the participant's HIV status. HIV-positive and HIV-negative men both engaged in sex with men of similar status more often than they engaged in sex with men known to be a different HIV status (i.e., serosorting). However, HIV-negative men disclosed their HIV-status with about half of their partners, whereas HIV-positive participants disclosed with only about one-third. With regard to strategic positioning, HIV-positive participants were the receptive partner about half the time with their HIV-negative partners and with their HIV-positive partners. In contrast, strategic positioning was very common among HIV-negative participants-they rarely bottomed with HIV-positive partners, bottomed about one-third of the time with status-unknown partners, and 42% of the time (on average) with HIV-negative partners. Highly sexually active GBMSM are a critical population in which to both investigate HIV prevention strategies as well as develop effective intervention programs. Providers and clinicians might be well served to include a wide range of behavioral harm reduction strategies in addition to condom use and biomedical approaches to reduce onward HIV transmission. PMID:26348322

  8. A Systematic Review of the Relationship between Socio-Economic Position and Physical Activity

    ERIC Educational Resources Information Center

    Gidlow, Christopher; Johnston, Lynne Halley; Crone, Diane; Ellis, Naomi; James, David

    2006-01-01

    Objective: The aim of the present review was to examine epidemiological evidence to determine if there is strong evidence of a positive gradient of increasing physical activity across the socio-economic strata, and how relationships are affected by socio-economic measurement. Design: Systematic review. Method: A search of major databases was…

  9. Positive Youth Development through an Outdoor Physical Activity Programme: Evidence from a Four-Year Evaluation

    ERIC Educational Resources Information Center

    Armour, Kathleen; Sandford, Rachel

    2013-01-01

    In 2006, Sandford, Armour and Warmington undertook a comprehensive review of the literature on the role of physical activity/sport and physical education in promoting positive development for disaffected youth. This paper revisits the findings of the literature review in light of data from a four-year evaluation of one corporate-sponsored physical…

  10. Enhanced Right Amygdala Activity in Adolescents during Encoding of Positively-Valenced Pictures

    PubMed Central

    Vasa, Roma A.; Pine, Daniel S.; Thorn, Julia M.; Nelson, Tess E.; Spinelli, Simona; Nelson, Eric; Maheu, Francoise S.; Ernst, Monique; Bruck, Maggie; Mostofsky, Stewart H.

    2010-01-01

    While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30 minutes later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period. PMID:21127721

  11. Positive Activities: Qualitative Research with Parents. Solutions Research. Research Report. DCSF-RR142

    ERIC Educational Resources Information Center

    Department for Children, Schools and Families, 2009

    2009-01-01

    This research was commissioned by COI and DCSF to understand in depth, the barriers, motivators and messages for parents to encourage participation in positive activities for young people. Within this the research was designed to understand the level of influence of parents in whether a young person participates/what a young person might…

  12. Physical Activity and Positive Youth Development: Impact of a School-Based Program

    ERIC Educational Resources Information Center

    Madsen, Kristine A.; Hicks, Katherine; Thompson, Hannah

    2011-01-01

    Background: Protective factors associated with positive youth development predict health and education outcomes. This study explored trends in these protective factors and in physical activity among low-income students, and determined the impact of a school-based youth development program on these trends. Methods: This study used a…

  13. Students' Use of Extra-Curricular Activities for Positional Advantage in Competitive Job Markets

    ERIC Educational Resources Information Center

    Roulin, Nicolas; Bangerter, Adrian

    2013-01-01

    With the rise of mass higher education, competition between graduates in the labour market is increasing. Students are aware that their degree will not guarantee them a job and realise they should add value and distinction to their credentials to achieve a positional advantage. Participation in extra-curricular activities (ECAs) is one such…

  14. Research on acupuncture points and cortical functional activation position in cats by infrared imaging detection

    NASA Astrophysics Data System (ADS)

    Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming

    2007-12-01

    The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.

  15. Assessing the Positive Influence of Music Activities in Community Development Programs

    ERIC Educational Resources Information Center

    Dillon, Steve

    2006-01-01

    This article describes a framework for assessing the positive influence of music activities in community development programs. It examines hybrid music, health and rich media approaches to creative case study with the purpose of developing more compelling evidence based advocacy that examines the claims of a causal link. This preliminary study…

  16. Influence of proline position upon the ion channel activity of alamethicin.

    PubMed Central

    Kaduk, C; Duclohier, H; Dathe, M; Wenschuh, H; Beyermann, M; Molle, G; Bienert, M

    1997-01-01

    Alamethicin, a 20-residue peptaibol, induces voltage-dependent ion channels in lipid bilayers according to the barrel-stave model. To study relationships between the proline-14-induced kink region and the channel-forming behavior of the peptide, a set of alamethicin analogs with proline incorporated at positions 11, 12, 13, 14, 15, 16, and 17, respectively, as well as an analog with alanine instead of proline at position 14 were synthesized. Macroscopic conductance experiments show that the voltage dependence of the peptides is conserved although slightly influenced, but the apparent mean number of monomers forming the channels is significantly reduced when proline is not located at position 14. This is confirmed in single-channel experiments. The analogs with proline next to position 14 (i.e., 13, 15, 16) show stable conductance levels, but of reduced number, which follows the order Alam-P14 > Alam-P15 > Alam-P16 > Alam-P13. This reduction in the number of levels is connected with changes in the lifetime of the channels. Analogs with proline at position 11, 12, or 17 produce erratic, extremely short-lived current events that could not be resolved. The changes in functional properties are related to structural properties as probed by circular dichroism. The results indicate that proline at position 14 results in optimal channel activity, whereas channels formed by the analogs bearing proline at different positions are considerably less stable. PMID:9129817

  17. Activity of the Aurora Kinase inhibitor VX-680 against Bcr/Abl positive acute lymphoblastic leukemias

    PubMed Central

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-01-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia-chromosome positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for treatment of Bcr/Abl positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and upon culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL. PMID:20388735

  18. Experimental study on active vibration control using genetic algorithm-based system identification and optimized positive position feedback

    NASA Astrophysics Data System (ADS)

    Orszulik, Ryan R.; Shan, Jinjun

    2012-12-01

    A genetic algorithm is implemented to identify the transfer function of an experimental system consisting of a flexible manipulator with a collocated piezoelectric sensor/actuator pair. A multi-mode positive position feedback controller is then designed based upon the identified transfer function. To this end, the same iteratively implemented genetic algorithm is used to optimize all controller parameters by minimization of the closed loop H∞-norm. The designed controller is then applied for vibration suppression on the experimental system.

  19. Active vibration suppression through positive acceleration feedback on a building-like structure: An experimental study

    NASA Astrophysics Data System (ADS)

    Enríquez-Zárate, J.; Silva-Navarro, G.; Abundis-Fong, H. F.

    2016-05-01

    This work deals with the structural and dynamic analysis of a building-like structure consisting of a three-story building with one active vibration absorber. The base of the structure is perturbed using an electromagnetic shaker, which provides forces with a wide range of excitation frequencies, including some resonance frequencies of the structure. One beam-column of the structure is coupled with a PZT stack actuator to reduce the vibrations. The overall mechanical structure is modeled using Euler-Lagrange methodology and validated using experimental modal analysis and Fine Element Method (FEM) techniques. The active control laws are synthesized to actively attenuate the vibration system response via the PZT stack actuator, caused by excitation forces acting on the base of the structure. The control scheme is obtained using Positive Acceleration Feedback (PAF) and Multiple Positive Acceleration Feedback (MPAF) to improve the closed-loop system response. Some experimental results are included to illustrate the overall system performance.

  20. Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

    NASA Astrophysics Data System (ADS)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2015-03-01

    Dynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll's coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

  1. Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

    PubMed Central

    Miendlarzewska, Ewa A.; Eryilmaz, Hamdi; Vuilleumier, Patrik

    2015-01-01

    Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. PMID:24603023

  2. A professional ethics learning module for use in co-operative education.

    PubMed

    Cates, Cheryl; Dansberry, Bryan

    2004-04-01

    The Professional Practice Program, also known as the co-operative education (co-op) program, at the University of Cincinnati (UC) is designed to provide eligible students with the most comprehensive and professional preparation available. Beginning with the Class of 2006, students in UC's Centennial Co-op Class will be following a new co-op curriculum centered around a set of learning outcomes Regardless of their particular discipline, students will pursue common learning outcomes by participating in the Professional Practice Program, which will cover issues of organizational culture, technology, professional ethics, and the integration of theory and practice. During their third co-op work term, students will complete a learning module on Professional Ethics. To complete the learning module students must familiarize themselves with the code of ethics for their profession, create a hypothetical scenario portraying an ethical dilemma that involves issues covered by the code, resolve the dilemma, and explain why their resolution is the best course of action based upon the code of ethics. A three-party assessment process including students, employers and faculty complete the module. PMID:15152866

  3. The divide within: Older active ICT users position themselves against different 'Others'.

    PubMed

    Kania-Lundholm, Magdalena; Torres, Sandra

    2015-12-01

    Although research into older people's internet usage patterns is rapidly growing, their understandings of digital technologies, particularly in relation to how these are informed by their understandings of aging and old age, remain unexplored. This is the case because research on older active ICT users tends to regard old age as an empirically interesting part of the life-course as opposed to a theoretically profuse source of information about why and how older people engage with digital technologies. This article explores - through focus group interviews with 30 older adults (aged 66-89) - the ways in which the social position of old age is used by older active ICT users in order to make sense of how and why they engage with these technologies. In this article, positioning theory is used to shed light on how the older people interviewed positioned themselves as 'active older users' in the interviews. The analysis brings to the fore the divide that older people themselves create as they discursively position themselves against different types of ICT users and non-users (young and old) when describing how and why they engage with digital technologies. PMID:26568212

  4. Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity

    PubMed Central

    Chen, Ronald JY; Chung, Tse-yu; Li, Feng-yin; Lin, Nan-hei; Tzen, Jason TC

    2009-01-01

    Aim: To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Methods: The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginsenosides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. Results: Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibitory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 position of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these positions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. Conclusion: The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhibition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure. PMID:19060914

  5. [Comparative urinary bactericidal activity of oral antibiotics against gram-positive pathogens].

    PubMed

    Bedenić, Branka; Budimir, Ana; Gverić, Ana; Plecko, Vanda; Vranes, Jasmina; Bubonja-Sonje, Marina; Kalenić, Smilja

    2012-01-01

    In routine bacteriological laboratories the antibacterial activity of antibiotics is determined by in vitro testing, usually by disk-diffusion test. However, in vitro testing does not always reflect antibacterial efficiency of antibiotics in vivo. In this investigation, the urine samples obtained in a single oral dose pharmacokinetic study were examined for their bactericidal activity against a range of relevant Gram-positive urinary tract pathogens. Urinary bactericidal activity of linezolid had been previously compared with ciprofloxacin but not with other oral antibiotics such as beta-lactams. Linezolid showed satisfactory urinary bactericidal titres throughout the whole testing period against all Gram-positive cocci. Fluoroquinolones displayed high and persisting levels of urinary bactericidal activity against staphylococci, but their activity against enterococci was weaker. According to the results of ex-vivo testing amoxycillin could be recommended only for infections caused by E. faecalis. Amoxycillin combined with clavulanic acid can be considered as a therapeutic option for infections caused by S. saprophyticus and E. faecalis. Older cephalosporins had high titres only against S. saprophyticus. Their drawback is a short elimination half-time in urine resulting in rapid decrease of urinary bactericidal titers during dosing interval. Furthermore, they do not show activity against enterococci due to their intrinsic resistance to cephalosporins. PMID:22930932

  6. Examining the Research Base on University Co-Operative Education in Light of the Neoliberal Challenge to Liberal Education

    ERIC Educational Resources Information Center

    Milley, Peter; Kovinthan, Thursica

    2014-01-01

    Debates have been taking place in higher education communities in Canada and other Anglo-American contexts between defenders of liberal education and promoters of neoliberalism. One development not addressed is the growth of co-operative education (co-op). The origins of co-op may reside in John Dewey's (1939, 1966) ideas about experience and…

  7. Co-operative Learning for Students with Difficulties in Learning: A Description of Models and Guidelines for Implementation

    ERIC Educational Resources Information Center

    Murphy, Ellen; Grey, Ian M.; Honan, Rita

    2005-01-01

    As part of a larger study regarding the inclusion of children with disabilities in mainstream classroom settings, Ellen Murphy, of the D Clin Psych programme at NUI Galway, with Ian Grey and Rita Honan, from Trinity College, Dublin, reviewed existing literature on co-operative learning in the classroom. In this article, they identify four models…

  8. Strategy-Based Development of Teacher Educators' ICT Competence through a Co-operative Staff Development Project

    ERIC Educational Resources Information Center

    Lavonen, Jari; Lattu, Matti; Juuti, Kalle; Meisalo, Veijo

    2006-01-01

    An ICT strategy and an implementation plan for teacher education were created in a co-operative process. Visions and expectations of staff members and students were registered by questionnaires and by making notes during sessions in which the strategy was created. Thereafter, an implementation document, where the staff development programme and…

  9. Environmental Co-Operatives as Instruments for Delivering Across-Farm Environmental and Rural Policy Objectives: Lessons for the UK

    ERIC Educational Resources Information Center

    Franks, J. R.; Mc Gloin, A.

    2007-01-01

    This paper assesses the potential of environmental co-operatives (EC) to deliver environmental benefits and an integrated and strengthened rural economy in the UK. It is based on research into Dutch EC, which have about 10,000 members, of which a quarter are non-farmers. The paper details the benefits EC have delivered to their members, the Dutch…

  10. Characteristics of Mother-Infant Communicative Interaction: Relations to the Ratings of Maternal Sensitivity and Infant Co-Operation

    ERIC Educational Resources Information Center

    Paavola, Leila; Kemppinen, Kaarina; Kunnari, Sari; Kumpulainen, Kirsti; Moilanen, Irma; Ebeling, Hanna

    2006-01-01

    The present article reports a study of communicative behaviour among mothers and infants who were grouped according to the ratings of sensitivity and co-operation, respectively. The participants were 27 Finnish-speaking mothers and their 10-month-old first-born infants (13 boys and 14 girls). The study is descriptive by nature, and the data were…

  11. Perceptions of Co-Operation and Collegiality by Participants of a One-Day Challenge Course Programme

    ERIC Educational Resources Information Center

    Wolfe, Brent D.; Dattilo, John

    2007-01-01

    While many studies have sought to understand challenge courses and their benefits, less emphasis has been focused on understanding participants' perceptions of these programmes. In this study, 16 adults working at a dental office attended a one-day challenge course programme designed to teach lessons about co-operation. Data were collected via "in…

  12. Student Perceptions of Social Learning Space: Designing and Implementing a Co-Operative Assessment Task in Pharmacology

    ERIC Educational Resources Information Center

    Moni, Roger W.; Depaz, Iris; Lluka, Lesley J.

    2008-01-01

    We report findings from a case study of co-operative, group-based assessment in Pharmacology for second-year undergraduates at The University of Queensland, Australia. Students enrolled in the 2005 Bachelor of Science and 2006 Bachelor of Pharmacy degree programs, were early users of the university's new Collaborative Teaching and Learning Centre…

  13. Passive damping to enhance active positioning of a prototype lithography platen

    SciTech Connect

    Segalman, D.J.; Kipp, R.L.; Gregory, D.L.

    1994-12-31

    A viscoelastic tuned-mass damper was used to suppress specific structural modes of a prototype lithography platen. The platen is magnetically levitated and it is repositioned and held in position by a closed-loop feedback control system. Important capabilities of the platen control system are precise positioning and rapid repositioning, which tend to require high frequency bandwidth. The high bandwidth excites structural vibration modes which are disruptive to the control system. The present work was to develop and demonstrate a means to suppress these modes using passive vibration damping techniques. The motivation is to increase the robustness of the platen positioning and control system by reducing unwanted modal accelerations excited by high control system bandwidth. Activities performed and discussed in this paper include the analytical design of viscoelastic tuned-mass dampers and the demonstration/testing of their effectiveness on the platen while levitated and controlled.

  14. Individual Public Transportation Accessibility is Positively Associated with Self-Reported Active Commuting

    PubMed Central

    Djurhuus, Sune; Hansen, Henning Sten; Aadahl, Mette; Glümer, Charlotte

    2014-01-01

    Background: Active commuters have lower risk of chronic disease. Understanding which of the, to some extent, modifiable characteristics of public transportation that facilitate its use is thus important in a public health perspective. The aim of the study was to examine the association between individual public transportation accessibility and self-reported active commuting, and whether the associations varied with commute distance, age, and gender. Methods: Twenty-eight thousand nine hundred twenty-eight commuters in The Capital Region of Denmark reported self-reported time spent either walking or cycling to work or study each day and the distance to work or study. Data were obtained from the Danish National Health Survey collected in February to April 2010. Individual accessibility by public transportation was calculated using a multi-modal network in a GIS. Multilevel logistic regression was used to analyze the association between accessibility, expressed as access area, and being an active commuter. Results: Public transport accessibility area based on all stops within walking and cycling distance was positively associated with being an active commuter. Distance to work, age, and gender modified the associations. Residing within 10 km commute distance and in areas of high accessibility was associated with being an active commuter and meeting the recommendations of physical activity. For the respondents above 29 years, individual public transportation accessibility was positively associated with being an active commuter. Women having high accessibility had significantly higher odds of being an active commuter compared to having a low accessibility. For men, the associations were insignificant. Conclusion: This study extends the knowledge about the driving forces of using public transportation for commuting by examining the individual public transportation accessibility. Findings suggest that transportation accessibility supports active commuting and planning

  15. Positively Valenced Stimuli Facilitate Creative Novel Metaphoric Processes by Enhancing Medial Prefrontal Cortical Activation

    PubMed Central

    Subramaniam, Karuna; Beeman, Mark; Faust, Miriam; Mashal, Nira

    2013-01-01

    A metaphor is a figure of speech in which a subject is symbolic of another unrelated object. In the present study, we examined neural patterns associated with both novel unfamiliar and conventional familiar metaphoric processing, and how these patterns are modulated by affective valence. Prior to fMRI scanning, participants received a list of word pairs (novel unfamiliar metaphors as well as conventional familiar metaphors) and were asked to denote the valence (positive, negative, or neutral) of each word pair. During scanning, participants had to decide whether the word pairs formed meaningful or meaningless expressions. Results indicate that participants were faster and more accurate at deciding that positively valenced metaphors were meaningful compared to neutral metaphors. These behavioral findings were accompanied by increased activation in the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and the right inferior parietal lobe (RIPL). Specifically, positively valenced novel unfamiliar metaphors elicited activation in these brain regions in addition to the left superior temporal gyrus when compared to neutral novel metaphors. We also found that the mPFC and PCC mediated the processing of positively valenced metaphors when compared to negatively valenced metaphors. Positively valenced conventional metaphors, however, elicited different neural signatures when contrasted with either neutral or negatively valenced conventional metaphors. Together, our results indicate that positively valenced stimuli facilitate creative metaphoric processes (specifically novel metaphoric processes) by mediating attention and cognitive control processes required for the access, integration, and selection of semantic associations via modulation of the mPFC. The present study is important for the development of neural accounts of emotion-cognition interactions required for creativity, language, and successful social functioning in general. PMID:23637686

  16. Identification of novel aminopiperidine derivatives for antibacterial activity against Gram-positive bacteria.

    PubMed

    Lee, Hee-Yeol; An, Kyung-Mi; Jung, Juyoung; Koo, Je-Min; Kim, Jeong-Geun; Yoon, Jong-Min; Lee, Myong-Jae; Jang, HyeonSoo; Lee, Hong-Sub; Park, Soobong; Kang, Jae-Hoon

    2016-07-01

    We have previously reported amidopiperidine derivatives as a novel peptide deformylase (PDF) inhibitor and evaluated its antibacterial activity against Gram-positive bacteria, but poor pharmacokinetic profiles have resulted in low efficacy in in vivo mouse models. In order to overcome these weaknesses, we newly synthesized aminopiperidine derivatives with remarkable antimicrobial properties and oral bioavailability, and also identified their in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP). PMID:27173797

  17. Dynamic detection of window starting positions and its implementation within an activity recognition framework.

    PubMed

    Ni, Qin; Patterson, Timothy; Cleland, Ian; Nugent, Chris

    2016-08-01

    Activity recognition is an intrinsic component of many pervasive computing and ambient intelligent solutions. This has been facilitated by an explosion of technological developments in the area of wireless sensor network, wearable and mobile computing. Yet, delivering robust activity recognition, which could be deployed at scale in a real world environment, still remains an active research challenge. Much of the existing literature to date has focused on applying machine learning techniques to pre-segmented data collected in controlled laboratory environments. Whilst this approach can provide valuable ground truth information from which to build recognition models, these techniques often do not function well when implemented in near real time applications. This paper presents the application of a multivariate online change detection algorithm to dynamically detect the starting position of windows for the purposes of activity recognition. PMID:27392647

  18. Graduated exposure and positive reinforcement to overcome setting and activity avoidance in an adolescent with autism.

    PubMed

    Schmidt, Jonathan D; Luiselli, James K; Rue, Hanna; Whalley, Katherine

    2013-01-01

    Some students who have developmental disabilities avoid settings and activities that can improve their learning and quality of life. This two-phase study concerned an adolescent boy with autism who avoided the gross-motor exercise room, gymnasium, and music room at his school; he demonstrated distress, agitation, and problem behaviors when prompted to enter these areas. Using graduated exposure combined with positive reinforcement, he learned to enter these settings without resisting and eventually to participate in activities within the settings. This article discusses this intervention approach for reducing and eliminating avoidant behavior. PMID:22987915

  19. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    PubMed Central

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-01-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis. PMID:27457620

  20. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    NASA Astrophysics Data System (ADS)

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-07-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis.

  1. TNF activation of NF-κB is essential for development of single-positive thymocytes.

    PubMed

    Webb, Louise V; Ley, Steven C; Seddon, Benedict

    2016-07-25

    NF-κB activation has been implicated at multiple stages of thymic development of T cells, during which it is thought to mediate developmental signals originating from the T cell receptor (TCR). However, the Card11-Bcl10-Malt1 (CBM) complex that is essential for TCR activation of NF-κB in peripheral T cells is not required for thymocyte development. It has remained unclear whether the TCR activates NF-κB independent of the CBM complex in thymocyte development or whether another NF-κB activating receptor is involved. In the present study, we generated mice in which T cells lacked expression of both catalytic subunits of the inhibitor of κB kinase (IKK) complex, IKK1 and IKK2, to investigate this question. Although early stages of T cell development were unperturbed, maturation of CD4 and CD8 single-positive (SP) thymocytes was blocked in mice lacking IKK1/2 in the T cell lineage. We found that IKK1/2-deficient thymocytes were specifically sensitized to TNF-induced cell death in vitro. Furthermore, the block in thymocyte development in IKK1/2-deficient mice could be rescued by blocking TNF with anti-TNF mAb or by ablation of TNFRI expression. These experiments reveal an essential role for TNF activation of NF-κB to promote the survival and development of single positive T cells in the thymus. PMID:27432943

  2. Petroleum geology of the Timor Gap Zone of co-operation (Area A)

    SciTech Connect

    Whittam, D.B. )

    1996-01-01

    The discovery of the Elang/Kakatua oilfield and Undan/Bayu gas-condensate accumulation has demonstrated the presence of a significant new hydrocarbon province in Area A of the Zone of Co-Operation between Australia and Indonesia (ZOCA). The western part of ZOCA is underlain by a north-west trending Triassic to mid-Cretaceous sag basin (the Northern Bonaparte Basin) which is overprinted by a series of east-west faults. The basin is related to Jurassic rifting and continental separation and is overlain by a seaward thickening, passive-margin wedge of Upper Cretaceous marls and Tertiary carbonates. The east-west faults form horst blocks which are the principal structural trapping style. Hydrocarbons have been encountered in fluvial and shallow marine sandstone of mid-Jurassic age (Bathonian to Callovian). These reservoirs are sealed by marine claystones and shales of Oxfordian to Berriasian age which are also potential petroleum source rocks containing a mixture of Type II and III organic matter. The discovered oils are very light (57[degrees] API), mature crudes with low producing gas/oil ratios. The understanding and prediction of the controls on reservoir quality and access to mature source rocks are key factors in the successful exploration of the area. Poor seismic data quality is a major obstacle to the accurate mapping of structure at the level of top reservoir. Several traps are interpreted to have failed due to breaching and remigration of hydrocarbons caused by Miocene/Pliocene faulting related to the collision between the Australasian and Eurasian plates.

  3. Petroleum geology of the Timor Gap Zone of co-operation (Area A)

    SciTech Connect

    Whittam, D.B.

    1996-12-31

    The discovery of the Elang/Kakatua oilfield and Undan/Bayu gas-condensate accumulation has demonstrated the presence of a significant new hydrocarbon province in Area A of the Zone of Co-Operation between Australia and Indonesia (ZOCA). The western part of ZOCA is underlain by a north-west trending Triassic to mid-Cretaceous sag basin (the Northern Bonaparte Basin) which is overprinted by a series of east-west faults. The basin is related to Jurassic rifting and continental separation and is overlain by a seaward thickening, passive-margin wedge of Upper Cretaceous marls and Tertiary carbonates. The east-west faults form horst blocks which are the principal structural trapping style. Hydrocarbons have been encountered in fluvial and shallow marine sandstone of mid-Jurassic age (Bathonian to Callovian). These reservoirs are sealed by marine claystones and shales of Oxfordian to Berriasian age which are also potential petroleum source rocks containing a mixture of Type II and III organic matter. The discovered oils are very light (57{degrees} API), mature crudes with low producing gas/oil ratios. The understanding and prediction of the controls on reservoir quality and access to mature source rocks are key factors in the successful exploration of the area. Poor seismic data quality is a major obstacle to the accurate mapping of structure at the level of top reservoir. Several traps are interpreted to have failed due to breaching and remigration of hydrocarbons caused by Miocene/Pliocene faulting related to the collision between the Australasian and Eurasian plates.

  4. Activity in ventromedial prefrontal cortex during self-related processing: positive subjective value or personal significance?

    PubMed

    Kim, Kyungmi; Johnson, Marcia K

    2015-04-01

    Well-being and subjective experience of a coherent world depend on our sense of 'self' and relations between the self and the environment (e.g. people, objects and ideas). The ventromedial prefrontal cortex (vMPFC) is involved in self-related processing, and disrupted vMPFC activity is associated with disruptions of emotional/social functioning (e.g. depression and autism). Clarifying precise function(s) of vMPFC in self-related processing is an area of active investigation. In this study, we sought to more specifically characterize the function of vMPFC in self-related processing, focusing on two alternative accounts: (i) assignment of positive subjective value to self-related information and (ii) assignment of personal significance to self-related information. During functional magnetic resonance imaging (fMRI), participants imagined owning objects associated with either their perceived ingroup or outgroup. We found that for ingroup-associated objects, vMPFC showed greater activity for objects with increased than decreased post-ownership preference. In contrast, for outgroup-associated objects, vMPFC showed greater activity for objects with decreased than increased post-ownership preference. Our findings support the idea that the function of vMPFC in self-related processing may not be to represent/evaluate the 'positivity' or absolute preference of self-related information but to assign personal significance to it based on its meaning/function for the self. PMID:24837477

  5. Triterpene sapogenin-polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains.

    PubMed

    Na, Heiya; Li, Xiangpeng; Zou, Cunbin; Wang, Chenhong; Wang, Chao; Liu, Keliang

    2016-07-01

    Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charged cell membranes and possess moderate antibacterial activities. In this study, we designed and synthesized a series of sapogenin-polyarginine conjugates in which the triterpene sapogenin moiety was covalently appended to the positively charged polyarginine via click chemistry. A clear synergistic effect was found, and the conjugates exhibited potent and selective antibacterial activity against Gram-positive strains. Among them, BAc-R3 was the most promising compound, which was also proven to be nontoxic toward mammalian cells as well as stable in plasma. The mechanism of BAc-R3 primarily involves an interaction with the bacterial membrane, similar to that of antimicrobial peptides (AMPs). This scaffold design opens an avenue for the further development of novel antibiotics comprised of the combination of a peptide and a natural product. PMID:27209170

  6. Litter effects on seedling establishment interact with seed position and earthworm activity.

    PubMed

    Donath, T W; Eckstein, R L

    2012-01-01

    Seedling establishment is influenced by litter cover and by seed predators, but little is known about interactions between these two factors. We tested their effects on emergence of five typical grassland species in a microcosm experiment. We manipulated the amounts of grass litter, seed sowing position and earthworm activity to determine whether: (i) the protective effect of litter against seed predation depends on cover amount and seed sowing position, i.e., on top or beneath litter; (ii) seed transport by earthworms changes the effect of seed sowing position on seedling emergence; and (iii) seeds transported into deeper soil layers by earthworms are still germinable. Litter cover and presence of earthworms lowered seedling emergence. The impact of seed position increased with seed size. Emergence of large-seeded species was reduced when sown on the surface. Additionally, we found an important seed position × earthworm interaction related to seed size. Emergence of large-seeded species sown on top of the litter was up to three times higher when earthworms were present than without earthworms. Earthworms also significantly altered the depth distribution of seeds in the soil and across treatments: on average 6% of seeds germinated after burial. In contrast to the seed position effect, we found no size effect on mobility and germinability of seeds after burial in the soil. Nevertheless, the fate of different-sized seeds may differ. While burial will remove large seeds from the regeneration pool, it may enhance seed bank build up in small-seeded species. Consequently, changes in the amount of litter cover and the invertebrate community play a significant role in plant community composition. PMID:21972886

  7. Respiratory Motion of The Heart and Positional Reproducibility Under Active Breathing Control

    SciTech Connect

    Jagsi, Reshma; Moran, Jean M.; Kessler, Marc L.; Marsh, Robin B. C; Balter, James M.; Pierce, Lori J. . E-mail: ljpierce@umich.edu

    2007-05-01

    Purpose: To reduce cardiotoxicity from breast radiotherapy (RT), innovative techniques are under investigation. Information about cardiac motion with respiration and positional reproducibility under active breathing control (ABC) is necessary to evaluate these techniques. Methods and Materials: Patients requiring loco-regional RT for breast cancer were scanned by computed tomography using an ABC device at various breath-hold states, before and during treatment. Ten patients were studied. For each patient, 12 datasets were analyzed. Mutual information-based regional rigid alignment was used to determine the magnitude and reproducibility of cardiac motion as a function of breathing state. For each scan session, motion was quantified by evaluating the displacement of a point along the left anterior descending artery (LAD) with respect to its position at end expiration. Long-term positional reproducibility was also assessed. Results: Displacement of the LAD was greatest in the inferior direction, moderate in the anterior direction, and lowest in the left-right direction. At shallow breathing states, the average displacement of LAD position was up to 6 mm in the inferior direction. The maximum displacement in any patient was 2.8 cm in the inferior direction, between expiration and deep-inspiration breath hold. At end expiration, the long-term reproducibility (SD) of the LAD position was 3 mm in the A-P, 6 mm in the S-I, and 4 mm in the L-R directions. At deep-inspiration breath hold, long-term reproducibility was 3 mm in the A-P, 7 mm in the S-I, and 3 mm in the L-R directions. Conclusions: These data demonstrate the extent of LAD displacement that occurs with shallow breathing and with deep-inspiration breath hold. This information may guide optimization studies considering the effects of respiratory motion and reproducibility of cardiac position on cardiac dose, both with and without ABC.

  8. Dual functional activity of semaphorin 3B is required for positioning the anterior commissure.

    PubMed

    Falk, Julien; Julien, Falk; Bechara, Ahmad; Fiore, Roberto; Nawabi, Homaira; Zhou, Heather; Hoyo-Becerra, Carolina; Bozon, Muriel; Rougon, Geneviève; Grumet, Martin; Püschel, Andreas W; Sanes, Joshua R; Castellani, Valérie

    2005-10-01

    Chemorepulsion by semaphorins plays a critical role during the development of neuronal projections. Although semaphorin-induced chemoattraction has been reported in vitro, the contribution of this activity to axon pathfinding is still unclear. Using genetic and culture models, we provide evidence that both attraction and repulsion by Sema3B, a secreted semaphorin, are critical for the positioning of a major brain commissural projection, the anterior commissure (AC). NrCAM, an immunoglobulin superfamily adhesion molecule of the L1 subfamily, associates with neuropilin-2 and is a component of a receptor complex for Sema3B and Sema3F. Finally, we show that activation of the FAK/Src signaling cascade distinguishes Sema3B-mediated attractive from repulsive axonal responses of neurons forming the AC, revealing a mechanism underlying the dual activity of this guidance cue. PMID:16202709

  9. Small-Activating RNA Can Change Nucleosome Positioning in Human Fibroblasts.

    PubMed

    Wang, Bin; Sun, Jing; Shi, Jiandong; Guo, Qing; Tong, Xiangrong; Zhang, Jin; Hu, Ningzhu; Hu, YunZhang

    2016-07-01

    RNA activation (RNAa) is a mechanism of positive gene expression regulation mediated by small-activating RNAs (saRNAs), which target gene promoters and have been used as tools to manipulate gene expression. Studies have shown that RNAa is associated with epigenetic modifications at promoter regions; however, it is unclear whether these modifications are the cause or a consequence of RNAa. In this study, we examined changes in nucleosome repositioning and the involvement of RNA polymerase II (RNAPII) in this process. We screened saRNAs for OCT4 (POU5F1), SOX2, and NANOG, and identified several novel saRNAs. We found that nucleosome positioning was altered after saRNA treatment and that the formation of nucleosome-depleted regions (NDRs) contributed to RNAa at sites of RNAPII binding, such as the TATA box, CpG islands (CGIs), proximal enhancers, and proximal promoters. Moreover, RNAPII appeared to be bound specifically to NDRs. These results suggested that changes in nucleosome positions resulted from RNAa. We thus propose a hypothesis that targeting promoter regions using exogenous saRNAs can induce the formation of NDRs, exposing regulatory binding sites to recruit RNAPII, a key component of preinitiation complex, and leading to increased initiation of transcription. PMID:26993320

  10. NK and CD4+ T cell co-operative immune responses correlate with control of disease in a macaque SIV infection model1

    PubMed Central

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Tuero, Iskra; Patterson, L. Jean; Robert-Guroff, Marjorie

    2012-01-01

    Control of infectious disease may be accomplished by successful vaccination, or by complex immunologic and genetic factors favoring antigen-specific multicellular immune responses. Using a rhesus macaque model, we evaluated antigen-specific T cell-dependent NK cell immune responses in SIV-infected macaques, designated controlling or non-controlling based on long-term chronic viremia levels, to determine if NK cell effector functions contribute to control of SIV infection. We observed that Gag stimulation of macaque PBMCs induced subset-specific NK cell responses in SIV-controlling, but not non-controlling animals, and that circulatory NK cell responses were dependent on antigen-specific IL-2 production by CD4+ central memory T cells. NK cell activation was blocked by anti-IL-2 neutralizing antibody and by CD4+ T cell depletion which abrogated the Gag-specific responses. Among tissue-resident cells, splenic and circulatory NK cells displayed similar activation profiles, whereas liver and mucosal NK cells displayed a decreased activation profile, similar in SIV controlling and non-controlling macaques. Lack of T cell-dependent NK cell function was rescued in SIV non-controlling macaques through drug-mediated control of viremia. Our results indicate that control of disease progression in SIV controlling macaques is associated with co-operation between antigen-specific CD4+ T cells and NK cell effector function, highlight the importance of such cell-to-cell co-operativity in adaptive immunity and suggest this interaction should be further investigated in HIV vaccine development and other prophylactic vaccine approaches. PMID:22798665

  11. Physical Activity in the Prevention of Benign Paroxysmal Positional Vertigo: Probable Association

    PubMed Central

    Bazoni, Jéssica Aparecida; Mendes, William Siqueira; Meneses-Barriviera, Caroline Luiz; Melo, Juliana Jandre; Costa, Viviane de Souza Pinho; Teixeira, Denilson de Castro; Marchiori, Luciana Lozza de Moraes

    2014-01-01

    Introduction Physical inactivity is an important risk factor for many age-related diseases and symptoms such as dizziness and vertigo. Objective The aim of the study was to investigate the possible association between benign paroxysmal positional vertigo (BPPV) and regular physical activity in elderly subjects. Methods This cross-sectional study included 491 elderly individuals who lived independently. Physical exercise was assessed through a questionnaire and BPPV by history and the Dix-Hallpike maneuver. Results The present study indicates no significant association between BPPV with lack of physical activity in men and in the total population. We have confirmed associations between BPPV with lack of physical activity in women (p = 0.01). Women with a sedentary lifestyle who do not practice physical activity are 2.62 more likely to have BPPV than those with regular physical activity. Conclusion These results highlight the importance of identifying risk factors for BPPV that can be modified through specific interventions. Regular physical activity is a lifestyle with potential to decrease the risk of vertigo in women. PMID:25992128

  12. Localization of Physical Activity in Primary School Children Using Accelerometry and Global Positioning System

    PubMed Central

    Bürgi, Rahel; Tomatis, Laura; Murer, Kurt; de Bruin, Eling D.

    2015-01-01

    Background Ecological approaches have highlighted the importance of the built environment as a factor affecting physical activity. However, knowledge on children’s activity patterns is still incomplete. Particularly, data on the spatial context of physical activity is limited, which limits the potential to design location-based interventions effectively. Using global positioning system (GPS) and accelerometry, this study aimed to identify locations where children engage in moderate-vigorous physical activity (MVPA). Methods Participants included 119 children (11–14 years, 57% girls) from public schools in Winterthur, Switzerland. During a regular school week between February and April 2013, children wore an accelerometer and GPS sensor for seven consecutive days. Time-matched accelerometer and GPS data was mapped with a geographic information system and each data point was assigned to one of seven defined activity settings. Both the absolute amount of MVPA and proportion of time in MVPA were calculated for every setting. Multilevel analyses accounting for the hierarchical structure of the data were conducted to investigate any gender differences. Results Children achieved most MVPA on streets (34.5%) and on school grounds (33.4%). The proportion children spent in MVPA was highest in recreational facilities (19.4%), at other schools (19.2%) and on streets (18.6%). Boys accumulated significantly more MVPA overall and on other school grounds (p < 0.05) and showed a significantly higher proportion of time in MVPA at own school and outside of Winterthur (p < 0.05). Conclusions The results indicate the importance of streets and school grounds as activity-promoting environments. The high use of streets may be an indicator for active transportation, which appears to contribute to an active lifestyle in both genders. In contrast, the school setting is more likely to encourage physical activity in boys. Recreational facilities seem to be conducive for MVPA among both

  13. Force-Based Puncture Detection and Active Position Holding for Assisted Retinal Vein Cannulation*

    PubMed Central

    Gonenc, Berk; Tran, Nhat; Riviere, Cameron N.; Gehlbach, Peter; Taylor, Russell H.; Iordachita, Iulian

    2016-01-01

    Retinal vein cannulation is a demanding procedure proposed to treat retinal vein occlusion by direct therapeutic agent delivery methods. Challenges in identifying the moment of venous puncture, achieving cannulation and maintaining cannulation during drug delivery currently limit the feasibility of the procedure. In this study, we respond to these problems with an assistive system combining a handheld micromanipulator, Micron, with a force-sensing microneedle. The integrated system senses the instant of vein puncture based on measured forces and the position of the needle tip. The system actively holds the cannulation device securely in the vein following cannulation and during drug delivery. Preliminary testing of the system in a dry phantom, stretched vinyl membranes, demonstrates a significant improvement in the total time the needle could be maintained stably inside of the vein. This was especially evident in smaller veins and is attributed to decreased movement of the positioned cannula following venous cannulation. PMID:27127804

  14. Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia

    PubMed Central

    Meijerink, Hinta; Wisaksana, Rudi; Lestari, Mery; Meilana, Intan; Chaidir, Lydia; van der Ven, Andre JAM; Alisjahbana, Bachti; van Crevel, Reinout

    2015-01-01

    Introduction Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU. Methods Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naïve adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay. Results Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p<0.001), more often received tuberculosis treatment during follow-up (adjusted HR=1.71; 95% CI: 1.25–2.35) and more often had bacteriologically confirmed tuberculosis (OR=1.67; 95% CI: 0.94–2.96). LTBI was equally prevalent among people with and without a history of IDU (29.1 vs. 30.4%, NS). The risk estimates did not change after adjustment for CD4 cell count or ART. Conclusions HIV-positive individuals with a history of IDU in Indonesia have more active tuberculosis, with similar rates of LTBI. Within the HIV clinic, LTBI screening and isoniazid preventive therapy may be prioritized to patients with a history of IDU. PMID:25690530

  15. The influence of substituents in 3-position on the activity of chroman-type potassium channel activators.

    PubMed

    Bergmann, R; Gericke, R

    1994-03-01

    Swern oxidation of chromanol 1 led to ketone 3 with concomitant chlorination of the adjacent 4-position. Using Leuckart conditions, chromanone 2 was converted to enamine 5.--4-Bromochromene-3-carbaldehyde 8, which was obtained by Vilsmeier-Arnold reaction from 7, turned out to be a suitable intermediate for the insertion of the pyridone residue. 3-Chloro derivatives 16 and 19 resulted on heating the mesylate or tosylate with LiCl in DMF. Bromination of chromene 20 led to 21.--All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats with a dose of 1 mg/kg. PMID:8179475

  16. Classical-quantum arbitrarily varying wiretap channel: Ahlswede dichotomy, positivity, resources, super-activation

    NASA Astrophysics Data System (ADS)

    Boche, Holger; Cai, Minglai; Deppe, Christian; Nötzel, Janis

    2016-08-01

    We establish the Ahlswede dichotomy for arbitrarily varying classical-quantum wiretap channels, i.e., either the deterministic secrecy capacity of the channel is zero, or it equals its randomness-assisted secrecy capacity. We analyze the secrecy capacity of these channels when the sender and the receiver use various resources. It turns out that randomness, common randomness, and correlation as resources are very helpful for achieving a positive secrecy capacity. We prove the phenomenon "super-activation" for arbitrarily varying classical-quantum wiretap channels, i.e., two channels, both with zero deterministic secrecy capacity, if used together allow perfect secure transmission.

  17. S-Nitrosylation Positively Regulates Ascorbate Peroxidase Activity during Plant Stress Responses1

    PubMed Central

    Yang, Huanjie; Mu, Jinye; Chen, Lichao; Feng, Jian; Hu, Jiliang; Li, Lei; Zhou, Jian-Min; Zuo, Jianru

    2015-01-01

    Nitric oxide (NO) and reactive oxygen species (ROS) are two classes of key signaling molecules involved in various developmental processes and stress responses in plants. The burst of NO and ROS triggered by various stimuli activates downstream signaling pathways to cope with abiotic and biotic stresses. Emerging evidence suggests that the interplay of NO and ROS plays a critical role in regulating stress responses. However, the underpinning molecular mechanism remains poorly understood. Here, we show that NO positively regulates the activity of the Arabidopsis (Arabidopsis thaliana) cytosolic ascorbate peroxidase1 (APX1). We found that S-nitrosylation of APX1 at cysteine (Cys)-32 enhances its enzymatic activity of scavenging hydrogen peroxide, leading to the increased resistance to oxidative stress, whereas a substitution mutation at Cys-32 causes the reduction of ascorbate peroxidase activity and abolishes its responsiveness to the NO-enhanced enzymatic activity. Moreover, S-nitrosylation of APX1 at Cys-32 also plays an important role in regulating immune responses. These findings illustrate a unique mechanism by which NO regulates hydrogen peroxide homeostasis in plants, thereby establishing a molecular link between NO and ROS signaling pathways. PMID:25667317

  18. Gramicidin A Mutants with Antibiotic Activity against Both Gram-Positive and Gram-Negative Bacteria.

    PubMed

    Zerfas, Breanna L; Joo, Yechaan; Gao, Jianmin

    2016-03-17

    Antimicrobial peptides (AMPs) have shown potential as alternatives to traditional antibiotics for fighting infections caused by antibiotic-resistant bacteria. One promising example of this is gramicidin A (gA). In its wild-type sequence, gA is active by permeating the plasma membrane of Gram-positive bacteria. However, gA is toxic to human red blood cells at similar concentrations to those required for it to exert its antimicrobial effects. Installing cationic side chains into gA has been shown to lower its hemolytic activity while maintaining the antimicrobial potency. In this study, we present the synthesis and the antibiotic activity of a new series of gA mutants that display cationic side chains. Specifically, by synthesizing alkylated lysine derivatives through reductive amination, we were able to create a broad selection of structures with varied activities towards Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Importantly, some of the new mutants were observed to have an unprecedented activity towards important Gram-negative pathogens, including Escherichia coli, Klebsiella pneumoniae and Psuedomonas aeruginosa. PMID:26918268

  19. Effects of Cycling Conditions of Active Material From Discharged Ni Positive Plates Studied by Inelastic Neutron Scattering Spectroscopy

    NASA Technical Reports Server (NTRS)

    Eckert, Juergen; Varma, Ravi; Diebolt, Lisa; Reid, Margaret

    1998-01-01

    The objectives of this presentation are: identify atomic-level signatures of electrochemical activity of the active material on the Ni positive plates of Ni-H2 batteries, relate finding to cycling conditions and histories, and develop INS spectroscopy as a non-destructive testing technique for the evaluation of Ni-positive plates of Ni-H2 batteries.

  20. An Action Research Report on Applying Co-Operative Learning Techniques in an Intensive English Reading Class in China

    ERIC Educational Resources Information Center

    Fu, Xiao

    2013-01-01

    This study is to examine whether the implementation of CL in an intensive reading class has a positive effect on improving the passive situation of students, whether it helps activate their enthusiasm for and ease their anxiety of participation in language class activities, and whether it is helpful to their improvement of English proficiency. The…

  1. Evaluation of a "no-cost" Internet technology-based system for teleradiology and co-operative work.

    PubMed

    Bergh, B; Schlaefke, A; Pietsch, M; García, I; Vogl, T J

    2003-02-01

    The aim of this study was to assess the suitability of a no-cost system based on standard Internet technology components for teleradiology. The system was composed of free software (communication, DICOM viewer, compression) and standard off-the-shelf hardware components. For different image (CR, CT, MR) and network types (LAN and ISDN) the File Transfer, Audio and Video Conference, and Co-operative Work properties were examined and compared with the literature referring to standard complete packages and dedicated teleradiology systems. The main advantages of the no-cost system are: price; ease of use; independence from specific hardware; and potential connection to any possible partner. The performance of the File Transfer and the Audio and Video Conference was comparable to the other system groups with slight disadvantages in the usability. For Co-operative Work the employed "application sharing" technology does not meet the clinical requirements, which applies identically to the standard complete packages. Here the specialized systems prove superior, although they are proprietary. With minimal restraints the evaluated no-cost solution can be used for File Transfer and Conference scenarios. The usage for Co-operative Work with ISDN is not recommended, unless for the purpose of gaining experience or when dealing with small amounts of cases or images. PMID:12599011

  2. Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients

    PubMed Central

    Tokutake, Takayoshi; Baba, Hisami; Shimada, Yuji; Takeda, Wataru; Sato, Keijiro; Hiroshima, Yuki; Kirihara, Takehiko; Shimizu, Ikuo; Nakazawa, Hideyuki; Kobayashi, Hikaru; Ishida, Fumihiro

    2016-01-01

    The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant. PMID:27355205

  3. Reproducibility of liver position using active breathing coordinator for liver cancer radiotherapy

    SciTech Connect

    Eccles, Cynthia; Brock, Kristy K.; Bissonnette, Jean-Pierre; Hawkins, Maria; Dawson, Laura A. . E-mail: laura.dawson@rmp.uhn.on.ca

    2006-03-01

    Purpose: To measure the intrabreath-hold liver motion and the intrafraction and interfraction reproducibility of liver position relative to vertebral bodies using an active breathing coordinator (ABC) in patients with unresectable liver cancer treated with hypofractionated stereotactic body radiation therapy (SBRT). Methods: Tolerability of ABC and organ motion during ABC was assessed using kV fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT scans in the ABC breath-hold position were acquired at simulation to estimate the volumetric intrafraction reproducibility of the liver relative to the vertebral bodies. In addition, preceding each radiation therapy fraction, with the liver immobilized using ABC, repeat anteroposterior (AP) megavoltage verification images were obtained. Off-line alignments were completed to determine intrafraction reproducibility (from repeat images obtained before one treatment) and interfraction reproducibility (from comparisons of the final image for each fraction with the AP) of diaphragm position relative to vertebral bodies. For each image set, the vertebral bodies were aligned, and the resultant craniocaudal (CC) offset in diaphragm position was measured. Liver position during ABC was also evaluated from kV fluoroscopy acquired at the time of simulation, kV fluoroscopy at the time of treatment, and from MV beam's-eye view movie loops acquired during treatment. Results: Twenty-one of 34 patients were screened to be suitable for ABC. The average free breathing range of these patients was 13 mm (range, 5-1 mm). Fluoroscopy revealed that the average maximal diaphragm motion during ABC breath-hold was 1.4 mm (range, 0-3.4 mm). The MV treatment movie loops confirmed diaphragm stability during treatment. For a measure of intrafraction reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in 14 patients was conducted. The average mean difference in the liver surface position was -0.9 mm, -0

  4. Co-operative agreements and the EU Water Framework Directive in conjunction with the Common Agricultural Policy

    NASA Astrophysics Data System (ADS)

    Heinz, I.

    2007-06-01

    This paper discusses the significance of voluntary arrangements for the water and agricultural policies in the European Union. The current implementation of the European Water Framework Directive (WFD) and the reform of the Common Agricultural Policy (CAP) require new approaches in water management. As many case studies have shown, co-operative agreements (CAs) between water companies, farmers and authorities can help to reduce environmental pressures on water bodies. The main reasons for that are: i) water companies are ready to advise and financially support farmers in changing production methods; ii) changes of farming practices are tailored to the site-specific requirements; iii) farmers and water companies are interested in minimising the costs and environmental pressures as they benefit, for example, from modernization of farming methods, and reductions in cost of water treatment, and iv) voluntarily agreed commitments to change farming practices are often stricter than statutory rules. Moreover, precautionary rather than remedial measures are preferred. Tackling diffuse pollution is one of the main concerns of the WFD. CAs can enhance the cost-effectiveness of actions within the programmes of measures so that good water status is achieved by 2015. In CAs all relevant stakeholders, located in catchment areas of agricultural usage, can be involved. Thus, they can help to foster integrated water resources management. In particular, disproportionate costs of changing farming practices can be identified. With regard to the recent CAP reform, financial support for farmers will be linked to compliance with environmental standards and further commitments. This concerns both direct payments and agri-environmental programmes. The experience gained in CAs can provide information on best agricultural practices. Informed farmers are more ready to meet environmental requirements. Because CAs implement the most cost-effective changes in farming practice, it can be assumed

  5. Co-operative agreements and the EU Water Framework Directive in conjunction with the Common Agricultural Policy

    NASA Astrophysics Data System (ADS)

    Heinz, I.

    2008-05-01

    This paper discusses the significance of voluntary arrangements for the water and agricultural policies in the European Union. The current implementation of the European Water Framework Directive (WFD) and the reform of the Common Agricultural Policy (CAP) require new approaches in water management. As many case studies have shown, co-operative agreements (CAs) between water companies, farmers and authorities can help to reduce environmental pressures on water bodies. The main reasons for that are: i) water companies are ready to advise and financially support farmers in changing production methods; ii) changes of farming practices are tailored to the site-specific requirements; iii) farmers and water companies are interested in minimising the costs and environmental pressures as they benefit, for example, from modernization of farming methods, and reductions in cost of water treatment, and iv) voluntarily agreed commitments to change farming practices are often stricter than statutory rules. Moreover, precautionary rather than remedial measures are preferred. Tackling diffuse pollution is one of the main concerns of the WFD. CAs can enhance the cost-effectiveness of actions within the programmes of measures so that good water status is achieved by 2015. In CAs all relevant stakeholders, located in catchment areas of agricultural usage, can be involved. Thus, they can help to foster integrated water resources management. In particular, disproportionate costs of changing farming practices can be identified. With regard to the recent CAP reform, financial support for farmers will be linked to compliance with environmental standards and further commitments. This concerns both direct payments and agri-environmental programmes. The experience gained in CAs can provide information on best agricultural practices. Informed farmers are more ready to meet environmental requirements. Because CAs implement the most cost-effective changes in farming practice, it can be assumed

  6. Gendered experiences of conflict and co-operation in heterosexual relations of Somalis in exile in Gothenburg, Sweden.

    PubMed

    Aden, A S; Dahlgren, L; Tarsitani, G

    2004-01-01

    Political upheaval and poverty at home has been forcing many Somalis to immigrate. These immigrants do not only leave their physical house, families, relatives, loved ones, friends, but also familiarities, culture, customs, and often they do end up in no man's land being between their own and new home culture. Available reports suggest that there are about 15,000 Somalis in Sweden and their majority came here from late 1989 to 1996. About one third these immigrants live in and around the city of Gothenburg. This paper explores and describes gendered experiences of conflict and co-operation in heterosexual relations of Somalis in exile in Gothenburg, Sweden. A qualitative sociological in-depth interviews with 6 women and 7 men was performed during May 1999 to January 2000. A follow up focus group interviews with 10 people (2 women and 8 men) was also carried on. The results show that both the Somali culture and Muslim religion do not support the children being taught sex education in schools or the names of the sex organs being pronounced other than to be used as metaphors. The girls, unlike their age group males, experience a very painful and terrifying process during childhood in which their self-esteem is downgraded by means of serious degrading traditional active violence such as female genital mutilation and visible virginity control. The narratives tell stories in which Somali women are degraded and expected to obey in situations characterised by their man's arbitrariness. They are subject to a very extensive form of social control, which is especially pronounced on issues regarding sexuality. Their integrity as women is, consequently set aside. When Somali refugees came to Sweden some of them came to adopt much of the modern lifestyle and cultural norm systems, preferable young people and some of the females. Relating to a new culture with its new expectations on the norm obedience also created changes in self-esteem. Exile situation tends to generate

  7. Two Active Forms of UDP-N-Acetylglucosamine Enolpyruvyl Transferase in Gram-Positive Bacteria

    PubMed Central

    Du, Wensheng; Brown, James R.; Sylvester, Daniel R.; Huang, Jianzhong; Chalker, Alison F.; So, Chi Y.; Holmes, David J.; Payne, David J.; Wallis, Nicola G.

    2000-01-01

    Gene sequences encoding the enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from many bacterial sources were analyzed. It was shown that whereas gram-negative bacteria have only one murA gene, gram-positive bacteria have two distinct genes encoding these enzymes which have possibly arisen from gene duplication. The two murA genes of the gram-positive organism Streptococcus pneumoniae were studied further. Each of the murA genes was individually inactivated by allelic replacement. In each case, the organism was viable despite losing one of its murA genes. However, when attempts were made to construct a double-deletion strain, no mutants were obtained. This indicates that both genes encode active enzymes that can substitute for each other, but that the presence of a MurA function is essential to the organism. The two genes were further cloned and overexpressed, and the enzymes they encode were purified. Both enzymes catalyzed the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetylglucosamine, confirming they are both active UDP-N-acetylglucosamine enolpyruvyl transferases. The catalytic parameters of the two enzymes were similar, and they were both inhibited by the antibiotic fosfomycin. PMID:10894720

  8. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

    PubMed Central

    Xavier, Guilherme M.; Patist, Amanda L.; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T.; Pedro Martinez-Barbera, Juan; Thavaraj, Selvam; Cobourne, Martyn T.; Andoniadou, Cynthia L.

    2015-01-01

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma. PMID:26411543

  9. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation.

    PubMed

    Xavier, Guilherme M; Patist, Amanda L; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T; Martinez-Barbera, Juan Pedro; Thavaraj, Selvam; Cobourne, Martyn T; Andoniadou, Cynthia L

    2015-01-01

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma. PMID:26411543

  10. Knowing good from bad: differential activation of human cortical areas by positive and negative outcomes.

    PubMed

    Nieuwenhuis, Sander; Slagter, Heleen A; von Geusau, Niels J Alting; Heslenfeld, Dirk J; Holroyd, Clay B

    2005-06-01

    Previous research has identified a component of the event-related brain potential (ERP), the feedback-related negativity, that is elicited by feedback stimuli associated with unfavourable outcomes. In the present research we used event-related functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) recordings to test the common hypothesis that this component is generated in the caudal anterior cingulate cortex. The EEG results indicated that our paradigm, a time estimation task with trial-to-trial performance feedback, elicited a large feedback-related negativity (FRN). Nevertheless, the fMRI results did not reveal any area in the caudal anterior cingulate cortex that was differentially activated by positive and negative performance feedback, casting doubt on the notion that the FRN is generated in this brain region. In contrast, we found a number of brain areas outside the posterior medial frontal cortex that were activated more strongly by positive feedback than by negative feedback. These included areas in the rostral anterior cingulate cortex, posterior cingulate cortex, right superior frontal gyrus, and striatum. An anatomically constrained source model assuming equivalent dipole generators in the rostral anterior cingulate, posterior cingulate, and right superior frontal gyrus produced a simulated scalp distribution that corresponded closely to the observed scalp distribution of the FRN. These results support a new hypothesis regarding the neural generators of the FRN, and have important implications for the use of this component as an electrophysiological index of performance monitoring and reward processing. PMID:15978024

  11. Kinetics of positive ions and electrically neutral active particles in afterglow in neon at low pressure

    NASA Astrophysics Data System (ADS)

    Pejović, Milić M.; Nešić, Nikola T.; Pejović, Momčilo M.

    2014-04-01

    Kinetics of positive ions and electrically neutral active particles formed during breakdown and successive discharge in neon-filled tube at 6.6 millibars pressure had been analyzed. This analysis was performed on the basis of mean value of electrical breakdown time delay t¯d dependence on afterglow period τ (memory curve). It was shown that positive ions are present in the 1μs < τ < 30 ms interval, which is manifested through t ¯d slow increase with the increase of τ. A rapid t¯d increase in the 30 ms < τ < 3 s interval is a consequence of significant decrease of positive ions concentration and dominant role in breakdown initiation have ground state nitrogen atoms, which further release secondary electrons from the cathode by catalytic recombination process. These atoms are formed during discharge by dissociation of ground state nitrogen molecules that are present as impurities in neon. For τ > 3 s, breakdown is initiated by cosmic rays and natural radioactivity. The increase of discharge current leads to decrease of t¯d due to the increase of positive ions concentration in inter electrode gap. The increase of applied voltage also decreases t¯d for τ > 30 ms due to the increase of the probability for initial electron to initiate breakdown. The presence of UV radiation leads to the decrease of t¯d due to the increased electron yield caused by photoelectrons. The influence of photoelectrons on breakdown initiation can be noticed for τ > 0.1 ms, while they dominantly determine t¯d for τ > 30 ms.

  12. Kinetics of positive ions and electrically neutral active particles in afterglow in neon at low pressure

    SciTech Connect

    Pejović, Milić M. Nešić, Nikola T.; Pejović, Momčilo M.

    2014-04-15

    Kinetics of positive ions and electrically neutral active particles formed during breakdown and successive discharge in neon-filled tube at 6.6 millibars pressure had been analyzed. This analysis was performed on the basis of mean value of electrical breakdown time delay t{sup ¯}{sub d} dependence on afterglow period τ (memory curve). It was shown that positive ions are present in the 1μs < τ < 30 ms interval, which is manifested through t{sup ¯}{sub d} slow increase with the increase of τ. A rapid t{sup ¯}{sub d} increase in the 30 ms < τ < 3 s interval is a consequence of significant decrease of positive ions concentration and dominant role in breakdown initiation have ground state nitrogen atoms, which further release secondary electrons from the cathode by catalytic recombination process. These atoms are formed during discharge by dissociation of ground state nitrogen molecules that are present as impurities in neon. For τ > 3 s, breakdown is initiated by cosmic rays and natural radioactivity. The increase of discharge current leads to decrease of t{sup ¯}{sub d} due to the increase of positive ions concentration in inter electrode gap. The increase of applied voltage also decreases t{sup ¯}{sub d} for τ > 30 ms due to the increase of the probability for initial electron to initiate breakdown. The presence of UV radiation leads to the decrease of t{sup ¯}{sub d} due to the increased electron yield caused by photoelectrons. The influence of photoelectrons on breakdown initiation can be noticed for τ > 0.1 ms, while they dominantly determine t{sup ¯}{sub d} for τ > 30 ms.

  13. Magnitudes of muscle activation of spine stabilizers, gluteals, and hamstrings during supine bridge to neutral position.

    PubMed

    Youdas, James W; Hartman, James P; Murphy, Brooke A; Rundle, Ashley M; Ugorowski, Jenna M; Hollman, John H

    2015-01-01

    The aim of this study was to compare the magnitude of selective core muscle activation during supine bridging to neutral exercises (three on a stable and three on an unstable surface). Surface EMG analysis was performed on the lumbar multifidus, gluteus medius, gluteus maximus, and hamstrings from 13 male and 13 female subjects. Lumbar multifidus recruitment was not influenced by exercise or condition and ranged between 29.2 and 35.9% of maximum voluntary isometric contraction (MVIC). Peak gluteus medius activation (42.0% MVIC) occurred in unstable single-leg bridge. Maximum recruitment of gluteus maximus (32.6% MVIC) appeared during stable single-leg bridge. Peak hamstring activation (59.6% MVIC) occurred during stable double-leg hamstring curl. Regardless of condition, hamstrings demonstrated high (51.9-59.6% MVIC) muscle recruitment during double-leg hamstring curls compared with the single-leg bridge or double-leg bridge. Various supine bridging to neutral exercises activated the hamstrings at levels conducive to strengthening, whereas recruitment of lumbar multifidus, gluteus medius, and gluteus maximus promoted endurance training. Clinically, we were unable to conclude the unstable support surface was preferable to the stable surface for boosting muscle recruitment of spine stabilizers, gluteals, and hamstring muscles during supine bridge to neutral position. PMID:25671354

  14. Randomized Controlled Trial of Positive Affect Induction to Promote Physical Activity After Percutaneous Coronary Intervention

    PubMed Central

    Peterson, Janey C.; Charlson, Mary E.; Hoffman, Zachary; Wells, Martin T.; Wong, Shing-Chiu; Hollenberg, James P.; Jobe, Jared B.; Boschert, Kathryn A.; Isen, Alice M.; Allegrante, John P.

    2013-01-01

    Background Within 1 year after percutaneous coronary intervention, more than 20% of patients experience new adverse events. Physical activity confers a 25% reduction in mortality; however, physical activity is widely underused. Thus, there is a need for more powerful behavioral interventions to promote physical activity. Our objective was to motivate patients to achieve an increase in expenditure of 336 kcal/wk or more at 12 months as assessed by the Paffenbarger Physical Activity and Exercise Index. Methods Two hundred forty-two patients were recruited immediately after percutaneous coronary intervention between October 2004 and October 2006. Patients were randomized to 1 of 2 groups. The patient education (PE) control group (n=118) (1) received an educational workbook, (2) received a pedometer, and (3) set a behavioral contract for a physical activity goal. The positive affect/self-affirmation (PA) intervention group (n=124) received the 3 PE control components plus (1) a PA workbook chapter, (2) bimonthly induction of PA by telephone, and (3) small mailed gifts. All patients were contacted with standardized bimonthly telephone follow-up for 12 months. Results Attrition was 4.5%, and 2.1% of patients died. Significantly more patients in the PA intervention group increased expenditure by 336 kcal/wk or more at 12 months, our main outcome, compared with the PE control group (54.9% vs 37.4%, P=.007). The PA intervention patients were 1.7 times more likely to reach the goal of a 336-kcal/wk or more increase by 12 months, controlling for demographic and psychosocial measures. In multivariate analysis, the PA intervention patients had nearly double the improvement in kilocalories per week at 12 months compared with the PE control patients (602 vs 328, P=.03). Conclusion Patients who receive PA intervention after percutaneous coronary intervention are able to achieve a sustained and clinically significant increase in physical activity by 12 months. Trial Registration

  15. Pharmacological activity of a Bv8 analogue modified in position 24

    PubMed Central

    Lattanzi, R; Sacerdote, P; Franchi, S; Canestrelli, M; Miele, R; Barra, D; Visentin, S; DeNuccio, C; Porreca, F; De Felice, M; Guida, F; Luongo, L; de Novellis, V; Maione, S; Negri, L

    2012-01-01

    BACKGROUND AND PURPOSE The amphibian peptide Bv8 induces potent nociceptive sensitization in rodents. Its mammalian homologue, prokineticin 2 (PROK2), is strongly up-regulated in inflamed tissues and is a major determinant in triggering inflammatory pain. Bv8 and PROK2 activate two closely related GPCRs, PK1 and PK2, in a relatively non-selective fashion. To characterize better the roles of the two receptors in hyperalgesia and to obtain ligands whose binding affinity and efficacy differed for the two receptors, we modified the Bv8 molecule in regions essential for receptor recognition and activation. EXPERIMENTAL APPROACH We modified the Bv8 molecule by substituting Trp in position 24 with Ala (A-24) and compared it with Bv8 for binding and activating PK1 and PK2 receptors in cell preparations and in affecting nociceptive thresholds in rodents. KEY RESULTS A-24 preferentially bound to PK2 receptors and activated them with a lower potency (5-fold) than Bv8. When systemically injected, A-24 induced Bv8-like hyperalgesia in rats and in mice, at doses 100 times higher than Bv8. Locally and systemically injected at inactive doses, A-24 antagonized Bv8-induced hyperalgesia. In rat and mouse models of inflammatory and post-surgical pain, A-24 showed potent and long-lasting anti-hyperalgesic activity. Unlike Bv8, A-24 increased β-endorphin levels in mouse brain. CONCLUSIONS AND IMPLICATIONS A-24 induced its anti-hyperalgesic effect in rodents by directly blocking nociceptor PK1 receptors and by activating the central opioid system and the descending pain control pathway through brain PK2 receptors. PMID:22122547

  16. Reconstructing liver shape and position from MR image slices using an active shape model

    NASA Astrophysics Data System (ADS)

    Fenchel, Matthias; Thesen, Stefan; Schilling, Andreas

    2008-03-01

    We present an algorithm for fully automatic reconstruction of 3D position, orientation and shape of the human liver from a sparsely covering set of n 2D MR slice images. Reconstructing the shape of an organ from slice images can be used for scan planning, for surgical planning or other purposes where 3D anatomical knowledge has to be inferred from sparse slices. The algorithm is based on adapting an active shape model of the liver surface to a given set of slice images. The active shape model is created from a training set of liver segmentations from a group of volunteers. The training set is set up with semi-manual segmentations of T1-weighted volumetric MR images. Searching for the optimal shape model that best fits to the image data is done by maximizing a similarity measure based on local appearance at the surface. Two different algorithms for the active shape model search are proposed and compared: both algorithms seek to maximize the a-posteriori probability of the grey level appearance around the surface while constraining the surface to the space of valid shapes. The first algorithm works by using grey value profile statistics in normal direction. The second algorithm uses average and variance images to calculate the local surface appearance on the fly. Both algorithms are validated by fitting the active shape model to abdominal 2D slice images and comparing the shapes, which have been reconstructed, to the manual segmentations and to the results of active shape model searches from 3D image data. The results turn out to be promising and competitive to active shape model segmentations from 3D data.

  17. Oxygenation, EMG and position sense during computer mouse work. Impact of active versus passive pauses.

    PubMed

    Crenshaw, A G; Djupsjöbacka, M; Svedmark, A

    2006-05-01

    We investigated the effects of active versus passive pauses implemented during computer mouse work on muscle oxygenation and EMG of the forearm extensor carpi radialis muscle, and on wrist position sense. Fifteen healthy female subjects (age: 19-24 years) performed a 60-min mouse-operated computer task, divided into three 20 min periods, on two occasions separated by 3-6 days. On one occasion a passive pause (subjects resting) was implemented at the end of each 20-min period, and on another occasion an active pause (subjects performed a number of high intensity extensions of the forearm) was implemented. Also at the end of each 20-min period, test contractions were conducted and subjective ratings of fatigue and stress were obtained. Another parameter of interest was total haemoglobin calculated as the summation of oxy-and deoxy-haemoglobin, since it reflects blood volume changes. The most interesting findings were an overall increasing trend in total haemoglobin throughout the mouse work (P<0.001), and that this trend was greater for the active pause as compared to the passive pause (P<0.01). These data were accompanied by an overall increase in oxygen saturation (P<0.001), with a tendency, albeit not significant, toward a higher increase for the active pause (P=0.13). EMG amplitude and median frequency tended to decrease (P=0.08 and 0.05, respectively) during the mouse work but was not different between pause types. Borg ratings of forearm fatigue showed an overall increase during the activity (P<0.001), but the perceptions of stress did not change. Position sense did not change due to the mouse work for either pause type. While increasing trends were found for both pause types, the present study lends support to the hypothesis of an enhancement in oxygenation and blood volume for computer mouse work implemented with active pauses. However, a presumption of an association between this enhancement and attenuated fatigue during the mouse work was not supported

  18. Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity

    PubMed Central

    Erceg, Jelena; Saunders, Timothy E.; Girardot, Charles; Devos, Damien P.; Hufnagel, Lars; Furlong, Eileen E. M.

    2014-01-01

    Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood. PMID:24391522

  19. Activity of T-DM1 in Her2-positive breast cancer brain metastases.

    PubMed

    Bartsch, Rupert; Berghoff, Anna S; Vogl, Ursula; Rudas, Margaretha; Bergen, Elisabeth; Dubsky, Peter; Dieckmann, Karin; Pinker, Katja; Bago-Horvath, Zsuzsanna; Galid, Arik; Oehler, Leopold; Zielinski, Christoph C; Gnant, Michael; Steger, Guenther G; Preusser, Matthias

    2015-10-01

    Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast cancer. Local treatment remains the standard of care but lapatinib plus capecitabine was recently established as systemic therapy option. Due to a disruption of the blood-brain/tumour-barrier at metastatic sites, even large molecules may penetrate into the central nervous system (CNS). Here, we report on the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon documented CNS progression after initial local treatment. Thus, this study allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every 12 weeks with MRI or whenever symptoms of disease progression occurred. Ten patients were included; in two asymptomatic subjects, T-DM1 was administered as primary therapy, while eight had progressive BM. All patients had received prior treatment with trastuzumab, six had already received lapatinib, and three pertuzumab as well. Three patients had partial remission of BM, and two patient had stable disease lasting for ≥6 months; two further patients had stable disease for <6 months while three progressed despite treatment. At 8.5 months median follow-up, intracranial PFS was 5 months, and median OS from initiation of T-DM1 was not reached. Local treatment of BM remains the standard of care; lapatinib plus capecitabine is currently the best established systemic therapy option. Still, T-DM1 apparently offers relevant clinical activity in BM and further investigation is warranted. PMID:26303828

  20. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells.

    PubMed

    Li, Yang; Li, Yi-Fei; Si, Chong-Zhan; Zhu, Yu-Hui; Jin, Yan; Zhu, Tong-Tong; Liu, Ming-Yuan; Liu, Guang-Yao

    2016-07-15

    Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus. PMID:27157859

  1. Trait positive and negative emotionality differentially associate with diurnal cortisol activity.

    PubMed

    Miller, Karissa G; Wright, Aidan G C; Peterson, Laurel M; Kamarck, Thomas W; Anderson, Barbara A; Kirschbaum, Clemens; Marsland, Anna L; Muldoon, Matthew F; Manuck, Stephen B

    2016-06-01

    Inter-individual variability in metrics of hypothalamic-pituitary-adrenocortical (HPA) activity, such as the slope of the diurnal decline in cortisol, cortisol awakening response (CAR), and total cortisol output, have been found to associate inversely with trait ratings of extraversion and positive affect (E/PA) and positively with neuroticism and negative affect (N/NA) in some, but not all, investigations. These inconsistencies may partly reflect varied intensity of cortisol sampling among studies and reliance on self-rated traits, which are subject to reporting biases and limitations of introspection. Here, we further examined dispositional correlates of HPA activity in 490 healthy, employed midlife volunteers (M age=43 years; 54% Female; 86% white). Trait ratings were requested from participants and 2 participant-elected informants using the Positive and Negative Affect Schedule (PANAS) and Extraversion and Neuroticism dimensions of NEO personality inventories. CAR was assessed as percent increase in cortisol levels from awakening to 30min after awakening; and the diurnal slope and total output of cortisol [Area Under the Curve (AUC)] were determined from cortisol measurements taken at awakening, +4 and +9h later, and bedtime, across 3 workdays. Structural equation modeling was used to estimate multi-informant E/PA and N/NA factors. We used 3days of measurement as indicators to model each of the three latent cortisol factors (slope, CAR, and AUC). With the two latent emotionality and three latent cortisol indices included there was good fit to the data (χ(2)(200)=278.38, p=0.0002; RMSEA=0.028, 90% CI=0.02-0.04; CFI/TLI=0.97/0.96; SRMR=0.04). After controlling for covariates (age, sex, race), results showed higher latent E/PA associated with a steeper diurnal slope (Standardized β=-0.19, p=0.02) and smaller CAR (Standardized β=-0.26, p=0.004), whereas N/NA did not associate with any cortisol metric (Standardized β's=-0.12 to 0.13, p's=0.10 to 0.53). These

  2. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects

    PubMed Central

    Johannesson, Elisabet; Ringström, Gisela; Abrahamsson, Hasse; Sadik, Riadh

    2015-01-01

    AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms. PMID:25593485

  3. Clusterless Decoding of Position From Multiunit Activity Using A Marked Point Process Filter

    PubMed Central

    Deng, Xinyi; Liu, Daniel F.; Kay, Kenneth; Frank, Loren M.; Eden, Uri T.

    2016-01-01

    Point process filters have been applied successfully to decode neural signals and track neural dynamics. Traditionally, these methods assume that multiunit spiking activity has already been correctly spike-sorted. As a result, these methods are not appropriate for situations where sorting cannot be performed with high precision such as real-time decoding for brain-computer interfaces. As the unsupervised spike-sorting problem remains unsolved, we took an alternative approach that takes advantage of recent insights about clusterless decoding. Here we present a new point process decoding algorithm that does not require multiunit signals to be sorted into individual units. We use the theory of marked point processes to construct a function that characterizes the relationship between a covariate of interest (in this case, the location of a rat on a track) and features of the spike waveforms. In our example, we use tetrode recordings, and the marks represent a four-dimensional vector of the maximum amplitudes of the spike waveform on each of the four electrodes. In general, the marks may represent any features of the spike waveform. We then use Bayes’ rule to estimate spatial location from hippocampal neural activity. We validate our approach with a simulation study and with experimental data recorded in the hippocampus of a rat moving through a linear environment. Our decoding algorithm accurately reconstructs the rat’s position from unsorted multiunit spiking activity. We then compare the quality of our decoding algorithm to that of a traditional spike-sorting and decoding algorithm. Our analyses show that the proposed decoding algorithm performs equivalently or better than algorithms based on sorted single-unit activity. These results provide a path toward accurate real-time decoding of spiking patterns that could be used to carry out content-specific manipulations of population activity in hippocampus or elsewhere in the brain. PMID:25973549

  4. Rethinking procrastination: positive effects of "active" procrastination behavior on attitudes and performance.

    PubMed

    Chu, Angela Hsin Chun; Choi, Jin Nam

    2005-06-01

    Researchers and practitioners have long regarded procrastination as a self-handicapping and dysfunctional behavior. In the present study, the authors proposed that not all procrastination behaviors either are harmful or lead to negative consequences. Specifically, the authors differentiated two types of procrastinators: passive procrastinators versus active procrastinators. Passive procrastinators are procrastinators in the traditional sense. They are paralyzed by their indecision to act and fail to complete tasks on time. In contrast, active procrastinators are a "positive" type of procrastinator. They prefer to work under pressure, and they make deliberate decisions to procrastinate. The present results showed that although active procrastinators procrastinate to the same degree as passive procrastinators, they are more similar to nonprocrastinators than to passive procrastinators in terms of purposive use of time, control of time, self-efficacy belief, coping styles, and outcomes including academic performance. The present findings offer a more sophisticated understanding of procrastination behavior and indicate a need to reevaluate its implications for outcomes of individuals. PMID:15959999

  5. Size controlled protein nanoemulsions for active targeting of folate receptor positive cells.

    PubMed

    Loureiro, Ana; Nogueira, Eugénia; Azoia, Nuno G; Sárria, Marisa P; Abreu, Ana S; Shimanovich, Ulyana; Rollett, Alexandra; Härmark, Johan; Hebert, Hans; Guebitz, Georg; Bernardes, Gonçalo J L; Preto, Ana; Gomes, Andreia C; Cavaco-Paulo, Artur

    2015-11-01

    Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size - the use of 5mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy. PMID:26241920

  6. Earthquake lights and the stress-activation of positive hole charge carriers in rocks

    USGS Publications Warehouse

    St-Laurent, F.; Derr, J.S.; Freund, F.T.

    2006-01-01

    Earthquake-related luminous phenomena (also known as earthquake lights) may arise from (1) the stress-activation of positive hole (p-hole) charge carriers in igneous rocks and (2) the accumulation of high charge carrier concentrations at asperities in the crust where the stress rates increase very rapidly as an earthquake approaches. It is proposed that, when a critical charge carrier concentration is reached, the p-holes form a degenerated solid state plasma that can break out of the confined rock volume and propagate as a rapidly expanding charge cloud. Upon reaching the surface the charge cloud causes dielectric breakdown at the air-rock interface, i.e. corona discharges, accompanied by the emission of light and high frequency electromagnetic radiation. ?? 2006 Elsevier Ltd. All rights reserved.

  7. Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells

    PubMed Central

    Lin, Congping; Schuster, Martin; Guimaraes, Sofia Cunha; Ashwin, Peter; Schrader, Michael; Metz, Jeremy; Hacker, Christian; Gurr, Sarah Jane; Steinberg, Gero

    2016-01-01

    Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ∼95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes. PMID:27251117

  8. Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.

    PubMed

    Scocchera, Eric; Reeve, Stephanie M; Keshipeddy, Santosh; Lombardo, Michael N; Hajian, Behnoush; Sochia, Adrienne E; Alverson, Jeremy B; Priestley, Nigel D; Anderson, Amy C; Wright, Dennis L

    2016-07-14

    Although classical, negatively charged antifolates such as methotrexate possess high affinity for the dihydrofolate reductase (DHFR) enzyme, they are unable to penetrate the bacterial cell wall, rendering them poor antibacterial agents. Herein, we report a new class of charged propargyl-linked antifolates that capture some of the key contacts common to the classical antifolates while maintaining the ability to passively diffuse across the bacterial cell wall. Eight synthesized compounds exhibit extraordinary potency against Gram-positive S. aureus with limited toxicity against mammalian cells and good metabolic profile. High resolution crystal structures of two of the compounds reveal extensive interactions between the carboxylate and active site residues through a highly organized water network. PMID:27437079

  9. Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells

    NASA Astrophysics Data System (ADS)

    Lin, Congping; Schuster, Martin; Guimaraes, Sofia Cunha; Ashwin, Peter; Schrader, Michael; Metz, Jeremy; Hacker, Christian; Gurr, Sarah Jane; Steinberg, Gero

    2016-06-01

    Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ~95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes.

  10. Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells.

    PubMed

    Lin, Congping; Schuster, Martin; Guimaraes, Sofia Cunha; Ashwin, Peter; Schrader, Michael; Metz, Jeremy; Hacker, Christian; Gurr, Sarah Jane; Steinberg, Gero

    2016-01-01

    Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ∼95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes. PMID:27251117

  11. Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells.

    PubMed

    Shen, Dong; Guo, Cheng-Cheng; Wang, Jing; Qiu, Zhi-Kun; Sai, Ke; Yang, Qun-Ying; Chen, Yin-Sheng; Chen, Fu-Rong; Wang, Jie; Panasci, Lawrence; Chen, Zhong-Ping

    2015-11-01

    Glioma is one of the most common primary tumors of the central nervous system in adults. Glioblastoma (GBM) is the most lethal type of glioma, whose 5-year survival is 9.8% at best. Glioma stem-like cells (GSCs) play an important role in recurrence and treatment resistance. MGMT is a DNA repair protein that removes DNA adducts and therefore attenuates treatment efficiency. It has been reported that interferon-α/β (IFN-α/β) downregulates the level of MGMT and sensitizes glioma cells to temozolomide. In the present study, we assessed whether IFN-α/β is able to sensitize GSCs to temozolomide by modulating MGMT expression. Upon the treatment of IFN-α/β, the efficacy of temozolomide against MGMT‑positive GSCs was markedly enhanced by combination treatment with IFN-α/β when compared with the temozolomide single agent group, and MGMT expression was markedly decreased at the same time. Further mechanistic study showed that IFN-α/β suppressed the NF-κB activity, which further mediated the sensitization of MGMT‑positive GSCs to temozolomide. Our data therefore demonstrated that the application of IFN-α/β is a promising agent with which to enhance temozolomide efficiency and reduce drug resistance, and our findings shed light on improving clinical outcomes and prolonging the survival of patients with malignant gliomas. PMID:26329778

  12. Activity of T-DM1 in HER-2 positive central nervous system breast cancer metastases

    PubMed Central

    Torres, Sofia; Maralani, Pejman; Verma, Sunil

    2014-01-01

    A 55-year-old woman with metastatic human epidermal growth factor receptor 2 (HER-2) positive breast cancer (BC) to the lungs and bones was diagnosed with central nervous system (CNS) metastases in November 2011. The MRI showed a right parietal lobe mass with adjacent leptomeningeal disease and several small bilateral cerebellar metastases. She was treated with whole brain irradiation (WBI), followed by capecitabine and lapatinib (December 2011-March 2013) and trastuzumab and lapatinib (May 2013-August 2013). Then, the brain MRI showed progression. In the absence of significant neurological symptoms, we postponed WBI and closely monitored for the development of neurological symptoms. Systemic treatment with trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab, was initiated in September 2013 to control systemic disease. Unexpectedly, after two cycles of treatment the brain MRI showed a decrease in size of CNS metastases. This case report suggests possible activity of T-DM1 in HER-2 positive BC with CNS metastases. PMID:25123575

  13. Refining Time-Activity Classification of Human Subjects Using the Global Positioning System

    PubMed Central

    Hu, Maogui; Li, Wei; Li, Lianfa; Houston, Douglas; Wu, Jun

    2016-01-01

    Background Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS) has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns. Methods Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel). Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data) to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods. Results Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking) to 99.90% (indoor). Specificities varied from 96.33% (indoor) to 99.98% (outdoor static). The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions. Conclusions The random forests classification model can achieve high accuracy for the four major time-activity

  14. Dab2IP Regulates Neuronal Positioning, Rap1 Activity and Integrin Signaling in the Developing Cortex.

    PubMed

    Qiao, Shuhong; Homayouni, Ramin

    2015-01-01

    Dab2IP (DOC-2/DAB2 interacting protein) is a GTPase-activating protein which is involved in various aspects of brain development in addition to its roles in tumor formation and apoptosis in other systems. In this study, we carefully examined the expression profile of Dab2IP and investigated its physiological role during brain development using a Dab2IP-knockdown (KD) mouse model created by retroviral insertion of a LacZ-encoding gene-trapping cassette. LacZ staining revealed that Dab2IP is expressed in the ventricular zone as well as the cortical plate and the intermediate zone. Immunohistochemical analysis showed that Dab2IP protein is localized in the leading process and proximal cytoplasmic regions of migrating neurons in the intermediate zone. Bromodeoxyuridine birth dating experiments in combination with immunohistochemical analysis using layer-specific markers showed that Dab2IP is important for proper positioning of a subset of layer II-IV neurons in the developing cortex. Notably, neuronal migration was not completely disrupted in the cerebral cortex of Dab2IP-KD mice and disruption of migration was not strictly layer specific. Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin signaling and somal translocation in the superficial layer of the cortical plate through integrin signaling. Therefore, we examined whether Rap1 and integrin signaling were affected in Dab2IP-KD brains. We found that Dab2IP-KD resulted in higher levels of activated Rap1 and integrin in the developing cortex. Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling. PMID:25721469

  15. The effect of tongue position and resulting vertical dimension on masticatory muscle activity. A cross-sectional study.

    PubMed

    Valdés, C; Gutiérrez, M; Falace, D; Astaburuaga, F; Manns, A

    2013-09-01

    The purpose of this study was to: (a) compare the tonic electromyographic (EMG) activity of the temporalis and masseter muscles between two tongue positions, (b) compare the vertical dimension (VD) resulting from each tongue position and (c) determine the influence of the VD on the tonic EMG activity for each tongue position. Thirty-three healthy dental students with natural dentition and bilateral molar support, between the ages of 18 and 22 years, with no prior history of oro-facial injury, or current or past pain in the jaw, mouth, or tongue participated in the study. Tonic masseteric and temporalis EMG activities were recorded using surface electrodes. Subjects were instructed to passively place the tongue either on the anterior hard palate or in the floor of the mouth. At each tongue position, the resulting EMG and VD were recorded. No significant difference in EMG activity was found for either the masseter (P-value = 0·5376) or temporalis muscle (P-value = 0·7410), between the two tongue positions. However, there was a significant difference in the VD resulting from the two different tongue positions, being greater with the tongue placed in the floor of the mouth. There was no statistically significant correlation between VD and EMG activity for both tongue positions. In spite of the lack of difference in the effect of both tongue positions on the masseteric and temporalis EMG activity, an increment of the VD was registered for the floor of mouth-tongue position. However, VD was not correlated with EMG activity for both tongue positions. PMID:23855557

  16. Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens.

    PubMed

    Zhanel, George G; Love, Riley; Adam, Heather; Golden, Alyssa; Zelenitsky, Sheryl; Schweizer, Frank; Gorityala, Bala; Lagacé-Wiens, Philippe R S; Rubinstein, Ethan; Walkty, Andrew; Gin, Alfred S; Gilmour, Matthew; Hoban, Daryl J; Lynch, Joseph P; Karlowsky, James A

    2015-02-01

    Tedizolid phosphate is a novel oxazolidinone prodrug (converted to the active form tedizolid by phosphatases in vivo) that has been developed and recently approved (June 2014) by the United States FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid is an oxazolidinone, but differs from other oxazolidinones by possessing a modified side chain at the C-5 position of the oxazolidinone nucleus which confers activity against certain linezolid-resistant pathogens and has an optimized C- and D-ring system that improves potency through additional binding site interactions. The mechanism of action of tedizolid is similar to other oxazolidinones and occurs through inhibition of bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA) of the 50S subunit of the ribosome. As with other oxazolidinones, the spontaneous frequency of resistance development to tedizolid is low. Tedizolid is four- to eightfold more potent in vivo than linezolid against all species of staphylococci, enterococci, and streptococci, including drug-resistant phenotypes such as MRSA and vancomycin-resistant enterococci (VRE) and linezolid-resistant phenotypes. Importantly, tedizolid demonstrates activity against linezolid-resistant bacterial strains harboring the horizontally transmissible cfr gene, in the absence of certain ribosomal mutations conferring reduced oxazolidinone susceptibility. With its half-life of approximately 12 h, tedizolid is dosed once daily. It demonstrates linear pharmacokinetics, has a high oral bioavailability of approximately 90 %, and is primarily excreted by the liver as an inactive, non-circulating sulphate conjugate. Tedizolid does not require dosage adjustment in patients with any degree of renal dysfunction or hepatic dysfunction. Studies in animals have demonstrated that the pharmacodynamic parameter most closely

  17. A novel method for measuring TBAb activity in TSAb- and TBAb-positive serum.

    PubMed

    Ochi, Yukio; Hachiya, Takashi; Arata, Naoko

    2015-01-01

    We reported a conversion assay in which thyroid blocking antibody (TBAb) function as thyroid stimulating antibody (TSAb). TBAb-bound porcine thyroid cells (PTC) were made by incubating TBAb(+) serum and PTC for 1 hour. When these TBAb-bound PTC were incubated 4 h with rabbit anti-human (h) IgG antibody (Ab), cAMP production was high, but when incubated with normal rabbit serum (NRS) cAMP production was low. TBAb-Mnoclonal Ab (MoAb) (KI-70) showed similar conversion. However, when TSAb-MoAb(M22) was assayed, anti-hIgG Ab-produced cAMP was lower than NRS-produced cAMP. When a mixture of M22 and KI-70 was assayed, anti-hIgG Ab-produced cAMP was higher than NRS. Thus, it is possible to determine existence of TBAb in TSAb(+)serum when anti-IgG Ab-produced cAMP is higher than NRS-produced cAMP. In this assay TBAb activity in TSAb(+)serum was scored as positive, gray zone and negative when the difference [anti-hIgG Ab-produced cAMP(%)-NRS-produced cAMP(%)] was >100%, 50-100% and <±50%, respectively. In TSAb(+)sera of Graves' patients with no treatment or anti-thyroid therapy, positive TBAb was 9% (3/33 )and 6.9% (5/72), and gray zone was 18 % (6/33) and 25% (18/72), respectively. A low prevelance of TBAb and low TBAb activity (<200% as cAMP) was found in these Graves' patients. A radioisotope treated Graves' patient showed existence of both TSAb and TBAb at 5 months (NRS, 800% cAMP and anti-IgGAb,1,350% cAMP), and highly positive TBAb (NRS, 180% cAMP and anti-hIgG Ab, 3,200% cAMP) at 30 months. This conversion assay is useful principally for TBAb determination but is also useful for TBAb determination in TSAb(+)serum. PMID:26299889

  18. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity.

    PubMed

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. PMID:27304076

  19. Moisture-uptake by the positive active material from the casting solvent and the ambient environment

    NASA Astrophysics Data System (ADS)

    Saharan, Vijay; Roberts, Jeffrey; Manev, Vesselin; Chia, Yee Ho; MacLean, Greg; McMullen, Steven R.

    It is widely recognized that the presence of residual moisture has significant detrimental effects on the performance of lithium ion batteries. Studies have shown that the positive active material can be a major source of moisture contributors to the overall cell moisture. The aim of the present study is to understand the factors affecting moisture uptake by the doped-lithium nickel cobalt oxide material from the casting solvent, acetone, and the ambient environment. As-is and the air-dried powders under various conditions (300 °C for 24 h, 500 °C for 8 h, and 500 °C for 24 h) were exposed to ambient and humid air for various lengths of time. Similarly, all these powders were exposed to extra dry (47 ppm) and wet (5789 ppm) acetone. Karl Fisher measurements at 160 °C and 290 °C show that humidity levels (80-85% relative humidity versus 20-25%) and the exposure times are the critical factors. Acetone wetness and the length of exposure in it do not contribute significantly to the moisture uptake by the active material. Cathode powder drying helps in minimizing the amount of moisture uptake from the environment.

  20. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity

    PubMed Central

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. DOI: http://dx.doi.org/10.7554/eLife.15460.001 PMID:27304076

  1. Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity.

    PubMed

    Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah E; Boyce, Steven; Zhang, Yuhang

    2016-08-01

    Bioengineering hair follicles using cells isolated from human tissue remains a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of growth factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and integrin α8. After a 2-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin compared to control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was up-regulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

  2. Indole trimers with antibacterial activity against Gram-positive organisms produced using combinatorial biocatalysis.

    PubMed

    McClay, Kevin; Mehboob, Shahila; Yu, Jerry; Santarsiero, Bernard D; Deng, Jiangping; Cook, James L; Jeong, Hyunyoung; Johnson, Michael E; Steffan, Robert J

    2015-12-01

    The I100V isoform of toluene-4-monooxygenase was used to catalyze the oxidative polymerization of anthranil and various indoles under mildly acidic conditions, favoring the production of trimers. Compounds produced in sufficient yield were purified and tested for their ability to inhibit the growth of B. anthracis, E. faecalis, L. monocytogenes, S. aureus, and in some cases, F. tularensis. 15 of the compounds displayed promising antibacterial activity (MIC < 5 µg/ml) against one or more of the strains tested, with the best MIC values being <0.8 µg/ml. All of these compounds had good selectivity, showing minimal cytotoxicity towards HepG2 cells. The structure was solved for six of the compounds that could be crystallized, revealing that minimally two classes of indole based trimers were produced. One compound class produced was a group of substituted derivatives of the natural product 2,2-bis(3-indolyl) indoxyl. The other group of compounds identified was classified as tryptanthrin-like compounds, all having multi-ring pendant groups attached at position 11 of tryptanthrin. One compound of particular interest, SAB-J85, had a structure that suggests that any compound, with a ring structure that can be activated by an oxygenase, might serve as a substrate for combinatorial biocatalysis. PMID:26112315

  3. Does the Dumbbell-Carrying Position Change the Muscle Activity in Split Squats and Walking Lunges?

    PubMed Central

    Lehnert, Michal; Zaatar, Amr M.Z.; Svoboda, Zdenek; Xaverova, Zuzana

    2015-01-01

    Abstract Stastny, P, Lehnert, M, Zaatar, AMZ, Svoboda, Z, and Xaverova, Z. Does the dumbbell-carrying position change the muscle activity in split squats and walking lunges? J Strength Cond Res 29(11): 3177–3187, 2015—The forward walking lunge (WL) and split squat (SSq) are similar exercises that have differences in the eccentric phase, and both can be performed in the ipsilateral or contralateral carrying conditions. This study aimed to determine the effects of dumbbell-carrying position on the kinematics and electromyographic (EMG) amplitudes of the gluteus medius (Gmed), vastus medialis (VM), vastus lateralis (VL), and biceps femoris during WLs and SSqs. The resistance-trained (RT) and the non–resistance-trained (NT) groups (both n = 14) performed ipsilateral WLs, contralateral WLs, ipsilateral SSqs, and contralateral SSqs in a randomized order in a simulated training session. The EMG amplitude, expressed as a percentage of the maximal voluntary isometric contraction (%MVIC), and the kinematics, expressed as the range of motion (ROM) of the hip and knee, were measured during 5 repetition maximum for both legs. The repeated measure analyses of variance showed significant differences between the RT and NT groups. The NT group showed a smaller knee flexion ROM (p < 0.001, η2 = 0.36) during both types of WLs, whereas the RT group showed a higher eccentric Gmed amplitude (p < 0.001, η2 = 0.46) during all exercises and a higher eccentric VL amplitude (p < 0.001, η2 = 0.63) during contralateral WLs. Further differences were found between contralateral and ipsilateral WLs in both the RT (p < 0.001, η2 = 0.69) and NT groups (p < 0.001, η2 = 0.80), and contralateral WLs resulted in higher eccentric Gmed amplitudes. Contralateral WLs highly activated the Gmed (90% MVIC); therefore, this exercise can increase the Gmed maximal strength. The ipsilateral loading condition did not increase the Gmed or VM activity in the RT or NT group. PMID:25968228

  4. The ePHD protein SPBP interacts with TopBP1 and together they co-operate to stimulate Ets1-mediated transcription.

    PubMed

    Sjøttem, Eva; Rekdal, Cecilie; Svineng, Gunbjørg; Johnsen, Sylvia Sagen; Klenow, Helle; Uglehus, Rebecca Dale; Johansen, Terje

    2007-01-01

    SPBP (Stromelysin-1 PDGF responsive element binding protein) is a ubiquitously expressed 220 kDa nuclear protein shown to enhance or repress the transcriptional activity of various transcription factors. A yeast two-hybrid screen, with the extended plant homeodomain (ePHD) of SPBP as bait, identified TopBP1 (topoisomerase II beta-binding protein 1) as a candidate interaction partner of SPBP. TopBP1 has eight BRCA1 carboxy-terminal (BRCT) domains and is involved in DNA replication, DNA damage responses and in the regulation of gene expression. The interaction between SPBP and TopBP1 was confirmed in vitro and in vivo, and was found to be mediated by the ePHD domain of SPBP and the BRCT6 domain of TopBP1. Both SPBP and TopBP1 enhanced the transcriptional activity of Ets1 on the c-myc P1P2- and matrix metalloproteinase-3 (MMP3) promoters. Together they displayed a more than additive effect. Both proteins were associated with these promoters. The involvement of TopBP1 was dependent on the serine 1159 phosphorylation site, known to be important for transcriptional activation. Depletion of endogenous SPBP by siRNA treatment reduced MMP3 secretion by 50% in phorbol ester-stimulated human fibroblasts. Taken together, our results show that TopBP1 and SPBP interact physically and functionally to co-operate as co-activators of Ets1. PMID:17913746

  5. The ePHD protein SPBP interacts with TopBP1 and together they co-operate to stimulate Ets1-mediated transcription

    PubMed Central

    Sjøttem, Eva; Rekdal, Cecilie; Svineng, Gunbjørg; Johnsen, Sylvia Sagen; Klenow, Helle; Uglehus, Rebecca Dale; Johansen, Terje

    2007-01-01

    SPBP (Stromelysin-1 PDGF responsive element binding protein) is a ubiquitously expressed 220 kDa nuclear protein shown to enhance or repress the transcriptional activity of various transcription factors. A yeast two-hybrid screen, with the extended plant homeodomain (ePHD) of SPBP as bait, identified TopBP1 (topoisomerase II β-binding protein 1) as a candidate interaction partner of SPBP. TopBP1 has eight BRCA1 carboxy-terminal (BRCT) domains and is involved in DNA replication, DNA damage responses and in the regulation of gene expression. The interaction between SPBP and TopBP1 was confirmed in vitro and in vivo, and was found to be mediated by the ePHD domain of SPBP and the BRCT6 domain of TopBP1. Both SPBP and TopBP1 enhanced the transcriptional activity of Ets1 on the c-myc P1P2- and matrix metalloproteinase-3 (MMP3) promoters. Together they displayed a more than additive effect. Both proteins were associated with these promoters. The involvement of TopBP1 was dependent on the serine 1159 phosphorylation site, known to be important for transcriptional activation. Depletion of endogenous SPBP by siRNA treatment reduced MMP3 secretion by 50% in phorbol ester-stimulated human fibroblasts. Taken together, our results show that TopBP1 and SPBP interact physically and functionally to co-operate as co-activators of Ets1. PMID:17913746

  6. Analysis on the Load Carrying Mechanism Integrated as Heterogeneous Co-operative Manipulator in a Walking Wheelchair

    NASA Astrophysics Data System (ADS)

    Rajay Vedaraj, I. S.; Jain, Ritika; Rao, B. V. A.

    2014-07-01

    After industrial robots came into existence during 1960, the technology of robotics with the design and analysis of robots in various forms in industries as well as in domestic applications were developed. Nowadays, along with the automotive sector the robots are producing a great impact in the form of quality and production rate to register their existence reliable in various other sectors also. Robotic technology has undergone various phase translations from being tortured as humanoids to the present day manipulators. Depending upon the various forms of its existence, robot manipulators are designed as serial manipulators and parallel manipulators. Individually both types can be proved effective though both have various drawbacks in design and the kinematic analysis. The versatility of robots can be increased by making them work in an environment where the same work volume is shared by more than one manipulator. This work volume can be identified as co-operative work volume of those manipulators. Here the interference of manipulators in the work volume of other manipulators is possible and is made obstacle free. The main advantage of co-operative manipulators is that when a number of independent manipulators are put together in a cooperative work envelope the efficiency and ability to perform tasks is greatly enhanced. The main disadvantage of the co-operative manipulators lies in the complication of its design even for a simple application, in almost all fields. In this paper, a cooperative design of robot manipulators to work in co-operative work environment is done and analysed for its efficacy. In the industrial applications when robotic manipulators are put together in more numbers, the trajectory planning becomes the tough task in the work cell. Proper design can remove the design defects of the cooperative manipulators and can be utilized in a more efficient way. In the proposed research paper an analysis is made on such a type of cooperative manipulator

  7. A Co-operative Inquiry Into Generating, Describing, and Transforming Knowledge About De-escalation Practices in Mental Health Settings.

    PubMed

    Berring, Lene Lauge; Hummelvoll, Jan Kåre; Pedersen, Liselotte; Buus, Niels

    2016-07-01

    De-escalation is concerned with managing violent behaviour without resorting to coercive measures. Co-operative Inquiry provided the conceptual basis for generating knowledge regarding de-escalation practices in acute mental health care settings. The research included service users and staff members as co-researchers and knowledge was generated in dynamic research cycles around an extended epistemology of knowing: experiential, presentational, propositional, and practical. Through this process, co-researchers became de-escalation learners, implementing de-escalation practices while transforming violence management. Neighbouring mental health communities' involvement strengthened the transformation process and assisted in validating the research results. PMID:27070499

  8. American College of Sports Medicine Position Stand. Exercise and physical activity for older adults.

    PubMed

    1998-06-01

    ACSM Position Stand on Exercise and Physical Activity for Older Adults. Med. Sci. Sports. Exerc., Vol. 30, No. 6, pp. 992-1008, 1998. By the year 2030, the number of individuals 65 yr and over will reach 70 million in the United States alone; persons 85 yr and older will be the fastest growing segment of the population. As more individuals live longer, it is imperative to determine the extent and mechanisms by which exercise and physical activity can improve health, functional capacity, quality of life, and independence in this population. Aging is a complex process involving many variables (e.g., genetics, lifestyle factors, chronic diseases) that interact with one another, greatly influencing the manner in which we age. Participation in regular physical activity (both aerobic and strength exercises) elicits a number of favorable responses that contribute to healthy aging. Much has been learned recently regarding the adaptability of various biological systems, as well as the ways that regular exercise can influence them. Participation in a regular exercise program is an effective intervention/ modality to reduce/prevent a number of functional declines associated with aging. Further, the trainability of older individuals (including octo- and nonagenarians) is evidenced by their ability to adapt and respond to both endurance and strength training. Endurance training can help maintain and improve various aspects of cardiovascular function (as measured by maximal VO2, cardiac output, and arteriovenous O2 difference), as well as enhance submaximal performance. Importantly, reductions in risk factors associated with disease states (heart disease, diabetes, etc.) improve health status and contribute to an increase in life expectancy. Strength training helps offset the loss in muscle mass and strength typically associated with normal aging. Additional benefits from regular exercise include improved bone health and, thus, reduction in risk for osteoporosis; improved

  9. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in Hiv-positive adults

    PubMed Central

    Shah, Maunank; Hanrahan, Colleen; Wang, Zhuo Yu; Dendukuri, Nandini; Lawn, Stephen D; Denkinger, Claudia M; Steingart, Karen R

    2016-01-01

    Background Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease. Objectives To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis).To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening). Search methods We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861). Selection criteria Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were

  10. Reduced intra-amygdala activity to positively valenced faces in adolescent schizophrenia offspring.

    PubMed

    Barbour, Tracy; Murphy, Eric; Pruitt, Patrick; Eickhoff, Simon B; Keshavan, Matcheri S; Rajan, Usha; Zajac-Benitez, Caroline; Diwadkar, Vaibhav A

    2010-11-01

    Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the baso-lateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population. PMID:20716480

  11. Detecting grizzly bear use of ungulate carcasses using global positioning system telemetry and activity data.

    PubMed

    Ebinger, Michael R; Haroldson, Mark A; van Manen, Frank T; Costello, Cecily M; Bjornlie, Daniel D; Thompson, Daniel J; Gunther, Kerry A; Fortin, Jennifer K; Teisberg, Justin E; Pils, Shannon R; White, P J; Cain, Steven L; Cross, Paul C

    2016-07-01

    Global positioning system (GPS) wildlife collars have revolutionized wildlife research. Studies of predation by free-ranging carnivores have particularly benefited from the application of location clustering algorithms to determine when and where predation events occur. These studies have changed our understanding of large carnivore behavior, but the gains have concentrated on obligate carnivores. Facultative carnivores, such as grizzly/brown bears (Ursus arctos), exhibit a variety of behaviors that can lead to the formation of GPS clusters. We combined clustering techniques with field site investigations of grizzly bear GPS locations (n = 732 site investigations; 2004-2011) to produce 174 GPS clusters where documented behavior was partitioned into five classes (large-biomass carcass, small-biomass carcass, old carcass, non-carcass activity, and resting). We used multinomial logistic regression to predict the probability of clusters belonging to each class. Two cross-validation methods-leaving out individual clusters, or leaving out individual bears-showed that correct prediction of bear visitation to large-biomass carcasses was 78-88 %, whereas the false-positive rate was 18-24 %. As a case study, we applied our predictive model to a GPS data set of 266 bear-years in the Greater Yellowstone Ecosystem (2002-2011) and examined trends in carcass visitation during fall hyperphagia (September-October). We identified 1997 spatial GPS clusters, of which 347 were predicted to be large-biomass carcasses. We used the clustered data to develop a carcass visitation index, which varied annually, but more than doubled during the study period. Our study demonstrates the effectiveness and utility of identifying GPS clusters associated with carcass visitation by a facultative carnivore. PMID:26971522

  12. Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions

    PubMed Central

    Young, Erica J.; Williams, Cedric L.

    2013-01-01

    Norepinephrine is released in the amygdala following negatively arousing learning conditions. This event initiates a cascade of changes including the transcription of activity-regulated cytoskeleton-associated protein (Arc) expression, an early-immediate gene associated with memory encoding. Recent evidence suggests that the valence of emotionally laden encounters may generate lateralized, as opposed to symmetric release of this transmitter in the right or left amygdala. It is currently not clear if valence-induced patterns of selective norepinephrine output across hemispheres are also reproduced in downstream pathways of cellular signaling necessary for memory formation. This question was addressed by determining if Arc expression is differentially distributed across the right and left amygdala following exposure to positively or negatively valenced learning conditions respectively. Male Sprague Dawley rats were randomly assigned to groups exposed to the Homecage only, five auditory tones only, or five auditory tones paired with footshock (0.35 mA) during Pavlovian fear conditioning. Western blot analysis revealed that Arc expression in the right amygdala was elevated significantly above that observed in the left amygdala 60 and 90 min following fear conditioning. Similarly, subjects exposed to a negatively valenced outcome consisting of an unexpected reduction in food rewards showed a greater level of Arc expression in only the right, but not left basolateral amygdala. Presenting a positively valenced event involving an unexpected increase in food reward magnitude following bar pressing, resulted in significantly greater Arc expression in the left, but not right basolateral amygdala (p < 0.01). These findings indicate that the valence of emotionally arousing learning conditions is reflected at later stages of synaptic plasticity involving the transcription of immediate early genes such as Arc. PMID:24367308

  13. Detecting grizzly bear use of ungulate carcasses using global positioning system telemetry and activity data

    USGS Publications Warehouse

    Ebinger, Michael R.; Haroldson, Mark A.; van Manen, Frank T.; Costello, Cecily M; Bjornlie, Daniel D; Thompson, Daniel J.; Gunther, Kerry A.; Fortin, Jennifer K.; Teisberg, Justin E.; Pils, Shannon R; White, P J; Cain, Steven L; Cross, Paul C.

    2016-01-01

    Global positioning system (GPS) wildlife collars have revolutionized wildlife research. Studies of predation by free-ranging carnivores have particularly benefited from the application of location clustering algorithms to determine when and where predation events occur. These studies have changed our understanding of large carnivore behavior, but the gains have concentrated on obligate carnivores. Facultative carnivores, such as grizzly/brown bears (Ursus arctos), exhibit a variety of behaviors that can lead to the formation of GPS clusters. We combined clustering techniques with field site investigations of grizzly bear GPS locations (n = 732 site investigations; 2004–2011) to produce 174 GPS clusters where documented behavior was partitioned into five classes (large-biomass carcass, small-biomass carcass, old carcass, non-carcass activity, and resting). We used multinomial logistic regression to predict the probability of clusters belonging to each class. Two cross-validation methods—leaving out individual clusters, or leaving out individual bears—showed that correct prediction of bear visitation to large-biomass carcasses was 78–88%, whereas the false-positive rate was 18–24%. As a case study, we applied our predictive model to a GPS data set of 266 bear-years in the Greater Yellowstone Ecosystem (2002–2011) and examined trends in carcass visitation during fall hyperphagia (September–October). We identified 1997 spatial GPS clusters, of which 347 were predicted to be large-biomass carcasses. We used the clustered data to develop a carcass visitation index, which varied annually, but more than doubled during the study period. Our study demonstrates the effectiveness and utility of identifying GPS clusters associated with carcass visitation by a facultative carnivore.

  14. Physical activity intensity can be accurately monitored by smartphone global positioning system 'app'.

    PubMed

    Gordon, Brett Ashley; Bruce, Lyndell; Benson, Amanda Clare

    2016-08-01

    Monitoring physical activity is important to better individualise health and fitness benefits. This study assessed the concurrent validity of a smartphone global positioning system (GPS) 'app' and a sport-specific GPS device with a similar sampling rate, to measure physical activity components of speed and distance, compared to a higher sampling sport-specific GPS device. Thirty-eight (21 female, 17 male) participants, mean age of 24.68, s = 6.46 years, completed two 2.400 km trials around an all-weather athletics track wearing GPSports Pro™ (PRO), GPSports WiSpi™ (WISPI) and an iPhone™ with a Motion X GPS™ 'app' (MOTIONX). Statistical agreement, assessed using t-tests and Bland-Altman plots, indicated an (mean; 95% LOA) underestimation of 2% for average speed (0.126 km·h(-1); -0.389 to 0.642; p < .001), 1.7% for maximal speed (0.442 km·h(-1); -2.676 to 3.561; p = .018) and 1.9% for distance (0.045 km; -0.140 to 0.232; p < .001) by MOTIONX compared to that measured by PRO. In contrast, compared to PRO, WISPI overestimated average speed (0.232 km·h(-1); -0.376 to 0.088; p < .001) and distance (0.083 km; -0.129 to -0.038; p < .001) by 3.5% whilst underestimating maximal speed by 2.5% (0.474 km·h(-1); -1.152 to 2.099; p < .001). Despite the statistically significant difference, the MOTIONX measures intensity of physical activity, with a similar error as WISPI, to an acceptable level for population-based monitoring in unimpeded open-air environments. This presents a low-cost, minimal burden opportunity to remotely monitor physical activity participation to improve the prescription of exercise as medicine. PMID:26505223

  15. Impact of Different Body Positions on Bioelectrical Activity of the Pelvic Floor Muscles in Nulliparous Continent Women

    PubMed Central

    Chmielewska, Daria; Stania, Magdalena; Sobota, Grzegorz; Kwaśna, Krystyna; Błaszczak, Edward; Taradaj, Jakub; Juras, Grzegorz

    2015-01-01

    We examined pelvic floor muscles (PFM) activity (%MVC) in twenty nulliparous women by body position during exercise as well as the activation of abdominal muscles and the gluteus maximus during voluntary contractions of the PFMs. Pelvic floor muscle activity was recorded using a vaginal probe during five experimental trials. Activation of transversus abdominis, rectus abdominis, and gluteus maximus during voluntary PFM contractions was also assessed. Significant differences in mean normalized amplitudes of baseline PFM activity were revealed between standing and lying (P < 0.00024) and lying and ball-sitting positions (P < 0.0053). Average peak, average time before peak, and average time after peak did not differ significantly during the voluntary contractions of the PFMs. Baseline PFM activity seemed to depend on the body position and was the highest in standing. Pelvic floor muscles activity during voluntary contractions did not differ by position in continent women. Statistically significant differences between the supine lying and sitting positions were only observed during a sustained 60-second contraction of the PFMs. PMID:25793212

  16. Impact of changed positive and negative task-related brain activity on word-retrieval in aging

    PubMed Central

    Meinzer, M.; Seeds, L.; Flaisch, T.; Harnish, S.; Cohen, M.L.; McGregor, K.; Conway, T.; Benjamin, M.; Crosson, B.

    2010-01-01

    Previous functional imaging studies that compared activity patterns in older and younger adults during non-linguistic tasks found evidence for two phenomena: older participants usually show more pronounced task-related positive activity in the brain hemisphere that is not dominant for the task and less pronounced negative task-related activity in temporo-parietal and midline brain regions. The combined effects of these phenomena and the impact on word-retrieval, however, have not yet been assessed. We used functional magnetic resonance imaging to explore task-related positive (active task > baseline) and negative activity (baseline > active task) during semantic and phonemic verbal fluency tasks. Increased right-frontal positive activity during the semantic task and reduced negative activity in the right hemisphere during both tasks was associated with reduced performance in older subjects. No substantial relationship between changes in positive and negative activity was observed in the older participants, pointing towards two partially independent but potentially co-occurring processes. Underlying causes of the observed functional network inefficiency during word-retrieval in older adults need to be determined in the future. PMID:20696496

  17. Does the Dumbbell-Carrying Position Change the Muscle Activity in Split Squats and Walking Lunges?

    PubMed

    Stastny, Petr; Lehnert, Michal; Zaatar, Amr M Z; Svoboda, Zdenek; Xaverova, Zuzana

    2015-11-01

    The forward walking lunge (WL) and split squat (SSq) are similar exercises that have differences in the eccentric phase, and both can be performed in the ipsilateral or contralateral carrying conditions. This study aimed to determine the effects of dumbbell-carrying position on the kinematics and electromyographic (EMG) amplitudes of the gluteus medius (Gmed), vastus medialis (VM), vastus lateralis (VL), and biceps femoris during WLs and SSqs. The resistance-trained (RT) and the non-resistance-trained (NT) groups (both n = 14) performed ipsilateral WLs, contralateral WLs, ipsilateral SSqs, and contralateral SSqs in a randomized order in a simulated training session. The EMG amplitude, expressed as a percentage of the maximal voluntary isometric contraction (%MVIC), and the kinematics, expressed as the range of motion (ROM) of the hip and knee, were measured during 5 repetition maximum for both legs. The repeated measure analyses of variance showed significant differences between the RT and NT groups. The NT group showed a smaller knee flexion ROM (p < 0.001, η = 0.36) during both types of WLs, whereas the RT group showed a higher eccentric Gmed amplitude (p < 0.001, η = 0.46) during all exercises and a higher eccentric VL amplitude (p < 0.001, η = 0.63) during contralateral WLs. Further differences were found between contralateral and ipsilateral WLs in both the RT (p < 0.001, η = 0.69) and NT groups (p < 0.001, η = 0.80), and contralateral WLs resulted in higher eccentric Gmed amplitudes. Contralateral WLs highly activated the Gmed (90% MVIC); therefore, this exercise can increase the Gmed maximal strength. The ipsilateral loading condition did not increase the Gmed or VM activity in the RT or NT group. PMID:25968228

  18. Frequencies of Inaudible High-Frequency Sounds Differentially Affect Brain Activity: Positive and Negative Hypersonic Effects

    PubMed Central

    Fukushima, Ariko; Yagi, Reiko; Kawai, Norie; Honda, Manabu; Nishina, Emi; Oohashi, Tsutomu

    2014-01-01

    The hypersonic effect is a phenomenon in which sounds containing significant quantities of non-stationary high-frequency components (HFCs) above the human audible range (max. 20 kHz) activate the midbrain and diencephalon and evoke various physiological, psychological and behavioral responses. Yet important issues remain unverified, especially the relationship existing between the frequency of HFCs and the emergence of the hypersonic effect. In this study, to investigate the relationship between the hypersonic effect and HFC frequencies, we divided an HFC (above 16 kHz) of recorded gamelan music into 12 band components and applied them to subjects along with an audible component (below 16 kHz) to observe changes in the alpha2 frequency component (10–13 Hz) of spontaneous EEGs measured from centro-parieto-occipital regions (Alpha-2 EEG), which we previously reported as an index of the hypersonic effect. Our results showed reciprocal directional changes in Alpha-2 EEGs depending on the frequency of the HFCs presented with audible low-frequency component (LFC). When an HFC above approximately 32 kHz was applied, Alpha-2 EEG increased significantly compared to when only audible sound was applied (positive hypersonic effect), while, when an HFC below approximately 32 kHz was applied, the Alpha-2 EEG decreased (negative hypersonic effect). These findings suggest that the emergence of the hypersonic effect depends on the frequencies of inaudible HFC. PMID:24788141

  19. TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.

    PubMed

    Nishimura, Kazuaki; Shindo, Satoru; Movila, Alexandru; Kayal, Rayyan; Abdullah, Albassam; Savitri, Irma Josefina; Ikeda, Atsushi; Yamaguchi, Tsuguno; Howait, Mohammed; Al-Dharrab, Ayman; Mira, Abdulghani; Han, Xiaozhe; Kawai, Toshihisa

    2016-08-01

    Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type. PMID:27343691

  20. In vitro activity of ceftaroline against mecC-positive MRSA isolates.

    PubMed

    Armengol-Porta, Marc; Tenorio-Abreu, Alberto; Bandt, Dirk; Coleman, David C; Gavier-Widen, Dolores; Hotzel, Helmut; Kinnevey, Peter; Lazaris, Alexandros; Peters, Martin; Rangstrup-Christensen, Lena; Schlotter, Katharina; Shore, Anna C; Ehricht, Ralf; Monecke, Stefan

    2016-06-01

    Ceftaroline is a new cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). A collection of 17 clinical and veterinary mecC-positive MRSA isolates was tested to evaluate the in vitro efficacy of ceftaroline against recently emerged mecC-MRSA isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of ceftaroline for the 17 isolates were determined by broth microdilution using the methodology and interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI). Additional susceptibility tests were performed using ceftaroline M.I.C.Evaluator (M.I.C.E.™) strips. All isolates showed susceptibility according to CLSI breakpoints, with MICs of ceftaroline ranging from 0.125mg/L to 0.25mg/L. MBCs were identical or up to a twofold dilution step higher. In conclusion, all tested isolates, from various sources and belonging to several clonal complexes (CCs), but predominantly to CC130, were found to be susceptible to ceftaroline. Ceftaroline could thus be an option for the treatment of mecC-MRSA infections. PMID:27436457

  1. Childhood socioeconomic position and adult leisure-time physical activity: a systematic review.

    PubMed

    Elhakeem, Ahmed; Cooper, Rachel; Bann, David; Hardy, Rebecca

    2015-01-01

    Regular leisure-time physical activity (LTPA) benefits health and is thought to be less prevalent in lower socioeconomic groups. Evidence suggests that childhood socioeconomic circumstances can impact on adult health and behaviour however, it is unclear if this includes an influence on adult LTPA. This review tested the hypothesis that a lower childhood socioeconomic position (SEP) is associated with less frequent LTPA during adulthood. Studies were located through a systematic search of MEDLINE, Embase, PsycINFO, CINAHL and SPORTDiscus and by searching reference lists. Eligible studies were English-language publications testing the association between any indicator of childhood SEP and an LTPA outcome measured during adulthood. Forty-five papers from 36 studies, most of which were European, were included. In most samples, childhood SEP and LTPA were self-reported in midlife. Twenty-two studies found evidence to support the review's hypothesis and thirteen studies found no association. Accounting for own adult SEP partly attenuated associations. There was more evidence of an association in British compared with Scandinavian cohorts and in women compared with men. Results did not vary by childhood SEP indicator or age at assessment of LTPA. This review found evidence of an association between less advantaged childhood SEP and less frequent LTPA during adulthood. Understanding how associations vary by gender and place could provide insights into underlying pathways. PMID:26138985

  2. Correlation of the highest-energy cosmic rays with the positions of nearby active galactic nuclei

    SciTech Connect

    Collaboration, The Pierre auger

    2007-12-01

    Data collected by the Pierre Auger Observatory provide evidence for anisotropy in the arrival directions of the cosmic rays with the highest energies, which are correlated with the positions of relatively nearby active galactic nuclei (AGN) [1]. The correlation has maximum significance for cosmic rays with energy greater than {approx} 6 x 10{sup 19} eV and AGN at a distance less than {approx} 75 Mpc. We have confirmed the anisotropy at a confidence level of more than 99% through a test with parameters specified a priori, using an independent data set. The observed correlation is compatible with the hypothesis that cosmic rays with the highest energies originate from extra-galactic sources close enough so that their flux is not significantly attenuated by interaction with the cosmic background radiation (the Greisen-Zatsepin-Kuzmin effect). The angular scale of the correlation observed is a few degrees, which suggests a predominantly light composition unless the magnetic fields are very weak outside the thin disk of our galaxy. Our present data do not identify AGN as the sources of cosmic rays unambiguously, and other candidate sources which are distributed as nearby AGN are not ruled out. We discuss the prospect of unequivocal identification of individual sources of the highest-energy cosmic rays within a few years of continued operation of the Pierre Auger Observatory.

  3. Frequencies of inaudible high-frequency sounds differentially affect brain activity: positive and negative hypersonic effects.

    PubMed

    Fukushima, Ariko; Yagi, Reiko; Kawai, Norie; Honda, Manabu; Nishina, Emi; Oohashi, Tsutomu

    2014-01-01

    The hypersonic effect is a phenomenon in which sounds containing significant quantities of non-stationary high-frequency components (HFCs) above the human audible range (max. 20 kHz) activate the midbrain and diencephalon and evoke various physiological, psychological and behavioral responses. Yet important issues remain unverified, especially the relationship existing between the frequency of HFCs and the emergence of the hypersonic effect. In this study, to investigate the relationship between the hypersonic effect and HFC frequencies, we divided an HFC (above 16 kHz) of recorded gamelan music into 12 band components and applied them to subjects along with an audible component (below 16 kHz) to observe changes in the alpha2 frequency component (10-13 Hz) of spontaneous EEGs measured from centro-parieto-occipital regions (Alpha-2 EEG), which we previously reported as an index of the hypersonic effect. Our results showed reciprocal directional changes in Alpha-2 EEGs depending on the frequency of the HFCs presented with audible low-frequency component (LFC). When an HFC above approximately 32 kHz was applied, Alpha-2 EEG increased significantly compared to when only audible sound was applied (positive hypersonic effect), while, when an HFC below approximately 32 kHz was applied, the Alpha-2 EEG decreased (negative hypersonic effect). These findings suggest that the emergence of the hypersonic effect depends on the frequencies of inaudible HFC. PMID:24788141

  4. Electrical Conductivity of Rocks and Dominant Charge Carriers. Part 1; Thermally Activated Positive Holes

    NASA Technical Reports Server (NTRS)

    Freund, Friedemann T.; Freund, Minoru M.

    2012-01-01

    The prevailing view in the geophysics community is that the electrical conductivity structure of the Earth's continental crust over the 5-35 km depth range can best be understood by assuming the presence of intergranular fluids and/or of intragranular carbon films. Based on single crystal studies of melt-grown MgO, magma-derived sanidine and anorthosite feldspars and upper mantle olivine, we present evidence for the presence of electronic charge carriers, which derive from peroxy defects that are introduced during cooling, under non-equilibrium conditions, through a redox conversion of pairs of solute hydroxyl arising from dissolution of H2O.The peroxy defects become thermally activated in a 2-step process, leading to the release of defect electrons in the oxygen anion sublattice. Known as positive holes and symbolized by h(dot), these electronic charge carriers are highly mobile. Chemically equivalent to O(-) in a matrix of O(2-) they are highly oxidizing. Being metastable they can exist in the matrix of minerals, which crystallized in highly reduced environments. The h(dot) are highly mobile. They appear to control the electrical conductivity of crustal rocks in much of the 5-35 km depth range.

  5. Relationship between position of brain activity and change in optical density for NIR imaging

    NASA Astrophysics Data System (ADS)

    Kashio, Yoshihiko; Ono, Muneo; Firbank, Michael; Schweiger, Martin; Arridge, Simon R.; Okada, Eiji

    2000-11-01

    Multi-channel NIR system can obtain the topographic image of brain activity. Since the image is reconstructed from the change in optical density measured with the source-detector pairs, it is important to reveal the volume of tissue sampled by each source-detector pair. In this study, the light propagation in three-dimensional adult head model is calculated by hybrid radiosity-diffusion method. The model is a layered slab which mimics the extra cerebral tissue (skin, skull), CSF and brain. The change in optical density caused by the absorption change in a small cylindrical region of 10 mm in diameter at various positions in the brain is calculated. The greatest change in optical density can be observed when the absorber is located in the middle of the source and detector. When the absorber is located just below the source or detector, the change in optical density is almost half of that caused by the same absorber in the midpoint. The light propagation in the brain is strongly affected by the presence of non-scattering layer and consequently sensitive region is broadly distributed on the brain surface.

  6. A new co-operative inversion strategy via fuzzy clustering technique applied to seismic and magnetotelluric data

    NASA Astrophysics Data System (ADS)

    Thong Kieu, Duy; Kepic, Anton

    2015-04-01

    Geophysical inversion produces very useful images of earth parameters; however, inversion results usually suffer from inherent non-uniqueness: many subsurface models with different structures and parameters can explain the measurements. To reduce the ambiguity, extra information about the earth's structure and physical properties is needed. This prior information can be extracted from geological principles, prior petrophysical information from well logs, and complementary information from other geophysical methods. Any technique used to constrain inversion should be able to integrate the prior information and to guide updating inversion process in terms of the geological model. In this research, we have adopted fuzzy c-means (FCM) clustering technique for this purpose. FCM is a clustering method that allows us to divide the model of physical parameters into a few clusters of representative values that also may relate to geological units based on the similarity of the geophysical properties. This exploits the fact that in many geological environments the earth is comprised of a few distinctive rock units with different physical properties. Therefore FCM can provide a platform to constrain geophysical inversion, and should tend to produce models that are geologically meaningful. FCM was incorporated in both separate and co-operative inversion processing of seismic and magnetotelluric (MT) data with petrophysical constraints. Using petrophysical information through FCM assists the inversion to build a reliable earth model. In this algorithm, FCM plays a role of guider; it uses the prior information to drive the model update process, and also forming an earth model filled with rocks units rather than smooth transitions when the boundary is in doubt. Where petrophysical information from well logs or core measurement is not locally available the cluster petrophysics may be solved for in inversion as well if some knowledge of how many distinctive geological exist. A

  7. Evaluation of the Unesco Associated Schools Project in Education for International Co-operation and Peace.

    ERIC Educational Resources Information Center

    Churchill, Stacy; Omari, Issa

    In accordance with a mandate from Unesco's 1978 General Conference, an evaluation methodology and instruments were devised to assess the Unesco Associated School's success in encouraging international peace and human rights. The background of this assessment project and a report of evaluation activities are presented in this document. The…

  8. Learning Network Design: A Methodology for the Construction of Co-operative Distance Learning Environments.

    ERIC Educational Resources Information Center

    Davies, Dick

    Learning Network Design (LND) is a socially oriented methodology for construction of cooperative distance learning environments. The paper advances a social constructivist approach to learning in which learning and teaching are seen as a process of active communication, interpretation, and negotiation; offers a view of information technology as a…

  9. A Propensity Score Matching Study of Participation in Community Activities: A Path to Positive Outcomes for Youth in New Zealand?

    ERIC Educational Resources Information Center

    O'Connor, Seini; Jose, Paul E.

    2012-01-01

    Extracurricular activities are important in many young people's lives and have been associated with positive academic, psychological, and social outcomes. However, most previous research has been limited to school-based activities in the North American context. This study expands existing literature by analyzing longitudinal data from more than…

  10. In Vitro Activities of the Ketolide HMR 3647 against Recent Gram-Positive Clinical Isolates and Haemophilus influenzae

    PubMed Central

    Barry, Arthur L.; Fuchs, Peter C.; Brown, Steven D.

    1998-01-01

    The ketolide HMR 3647 (previously RU 66647) was evaluated against 2,563 recent clinical isolates of gram-positive pathogens and 200 Haemophilus influenzae isolates. HMR 3647 was active against macrolide-resistant streptococci, including pneumococci, but was not active against macrolide- or lincosamide-resistant staphylococci. Against H. influenzae, the potency of HMR 3647 was similar to that of azithromycin. PMID:9687424

  11. Recombinant expression of rat glycine N-methyltransferase and evidence for contribution of N-terminal acetylation to co-operative binding of S-adenosylmethionine.

    PubMed

    Ogawa, H; Gomi, T; Takata, Y; Date, T; Fujioka, M

    1997-10-15

    An expression vector was constructed that produced rat glycine N-methyltransferase in Escherichia coli. Recombinant glycine N-methyltransferase was purified to homogeneity by DEAE-cellulose and gel-filtration chromatography, with a yield of more than 80 mg of pure enzyme from a 1 litre culture. HPLC of tryptic peptides and analysis of isolated peptides showed that the recombinant enzyme was structurally identical with the liver enzyme except for the absence of N-terminal blocking. The alpha-amino group of rat glycine N-methyltransferase is blocked by acetylation [Ogawa, Konishi, Takata, Nakashima and Fujioka (1987) Eur. J. Biochem. 168, 141-151]. In contrast with the liver enzyme, which shows sigmoidal kinetics toward S-adenosylmethionine at all pH values tested [Ogawa and Fujioka (1982) J. Biol. Chem. 257, 3447-3452], the recombinant enzyme exhibited hyperbolic kinetics at low pH and sigmoidal rate behaviour at high pH. The Hill coefficient increased with increasing pH and a pKa of 8.11 was obtained in this transition. The values of Vmax and Km for glycine were not different between the two enzymes. These results suggest that elimination of the positive charge at the N-terminal end either by acetylation or deprotonation is required for co-operative behaviour. PMID:9359408

  12. In Vitro and In Vivo Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae.

    PubMed

    Morinaka, Akihiro; Tsutsumi, Yuko; Yamada, Keiko; Takayama, Yoshihiro; Sakakibara, Shiro; Takata, Toshihiko; Abe, Takao; Furuuchi, Takeshi; Inamura, Seiichi; Sakamaki, Yoshiaki; Tsujii, Nakako; Ida, Takashi

    2016-05-01

    Gram-negative bacteria are evolving to produce β-lactamases of increasing diversity that challenge antimicrobial chemotherapy. OP0595 is a new diazabicyclooctane serine β-lactamase inhibitor which acts also as an antibiotic and as a β-lactamase-independent β-lactam "enhancer" against Enterobacteriaceae Here we determined the optimal concentration of OP0595 in combination with piperacillin, cefepime, and meropenem, in addition to the antibacterial activity of OP0595 alone and in combination with cefepime, in in vitro time-kill studies and an in vivo infection model against five strains of CTX-M-15-positive Escherichia coli and five strains of KPC-positive Klebsiella pneumoniae An OP0595 concentration of 4 μg/ml was found to be sufficient for an effective combination with all three β-lactam agents. In both in vitro time-kill studies and an in vivo model of infection, cefepime-OP0595 showed stronger efficacy than cefepime alone against all β-lactamase-positive strains tested, whereas OP0595 alone showed weaker or no efficacy. Taken together, these data indicate that combinational use of OP0595 and a β-lactam agent is important to exert the antimicrobial functions of OP0595. PMID:26953205

  13. Co-operative roles for DNA supercoiling and nucleoid-associated proteins in the regulation of bacterial transcription.

    PubMed

    Dorman, Charles J

    2013-04-01

    DNA supercoiling and NAPs (nucleoid-associated proteins) contribute to the regulation of transcription of many bacterial genes. The horizontally acquired SPI (Salmonella pathogenicity island) genes respond positively to DNA relaxation, they are activated and repressed by the Fis (factor for inversion stimulation) and H-NS (histone-like nucleoid-structuring) NAPs respectively, and are positively controlled by the OmpR global regulatory protein. The ompR gene is autoregulated and responds positively to DNA relaxation. Binding of the Fis and OmpR proteins to their targets in DNA is differentially sensitive to its topological state, whereas H-NS binds regardless of the topological state of the DNA. These data illustrate the overlapping and complex nature of NAP and DNA topological contributions to transcription control in bacteria. PMID:23514151

  14. The effect of co-stabilizer muscle activation on knee joint position sense: a single group pre-post test

    PubMed Central

    Nam, Yeongyo; Lee, Ho Jun; Choi, Myongryol; Chung, Sangmi; Park, Junhyung; Yu, Jaeho

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effect of co-stabilizer muscle activation on knee joint position sense. [Subjects and Methods] This study was a pre-post, single-blinded randomly controlled trial (angle sequence randomly selected) design. Seven healthy adults with no orthopaedic or neurological problems participated in this study. Knee joint position sense was measured by a target matching test at target angles of 30°, 45° and 80° of knee flexion a using digital inclinometer under two conditions: erect sitting, which is known to highly activate co-stabilizer muscle and slump sitting, which is known to little activate the co-stabilizer muscle. [Results] A significant difference in joint position matching error at the knee flexion angle of 45° was founded between two conditions erect sitting: (3.83 ± 1.47) and slump sitting: (1.00 ± 0.63). There were no significant differences in joint position matching error at the other target angles. [Conclusion] Knee joint position sense at 45° is likely to be affected by activation of co-stabilizer muscle, and this value is suitable for facilitation of joint position sense with skilled movement. PMID:27512279

  15. Effects of Positive and Negative Mood Induction on the Prefrontal Cortex Activity Measured by Near Infrared Spectroscopy.

    PubMed

    Compare, A; Brugnera, Agostino; Adorni, R; Sakatani, K

    2016-01-01

    The neurophysiological mechanism of positive versus negative emotions is insufficiently understood. In the present study, we examined the effect of event recall tasks on the prefrontal cortex (PFC) activity using near infrared spectroscopy (NIRS). Nine healthy adults were instructed to recall episodes of their life associated with positive (happiness) and negative (anger) emotion, both silently and verbally. Heart rate (HR) changes were simultaneously measured. NIRS showed an increased oxyhemoglobin (oxy-Hb) in the bilateral PFC during silent and verbal recall of both positive and negative episodes. The changes of oxy-Hb in the bilateral PFC during silent recall of negative episodes were significantly larger than those during silent recall of positive episodes (p < 0.01). There was no difference in average changes of oxy-Hb between silent and verbal recall of negative episodes (p > 0.95), while changes of oxy-Hb during verbal recall of positive episodes were larger than those during silent recall of positive episodes (p < 0.05). Both verbal and silent recall of positive and negative episodes increased HR; however, verbal recall caused larger increases of HR than silent recall (p < 0.01). The present results suggest that recall of negative episodes affect the PFC activity, which plays a key role in cognitive control of emotions, more than positive episodes. PMID:27526137

  16. In Vitro Activity of Ozenoxacin against Quinolone-Susceptible and Quinolone-Resistant Gram-Positive Bacteria

    PubMed Central

    López, Y.; Tato, M.; Espinal, P.; Garcia-Alonso, F.; Gargallo-Viola, D.; Cantón, R.

    2013-01-01

    In vitro activity of ozenoxacin, a novel nonfluorinated topical (L. D. Saravolatz and J. Leggett, Clin. Infect. Dis. 37:1210–1215, 2003) quinolone, was compared with the activities of other quinolones against well-characterized quinolone-susceptible and quinolone-resistant Gram-positive bacteria. Ozenoxacin was 3-fold to 321-fold more active than other quinolones. Ozenoxacin could represent a first-in-class nonfluorinated quinolone for the topical treatment of a broad range of dermatological infections. PMID:24080666

  17. UMP kinase from Streptococcus pneumoniae: evidence for co-operative ATP binding and allosteric regulation

    PubMed Central

    2004-01-01

    UMP kinase catalyses the phosphorylation of UMP by ATP to yield UDP and ADP. In prokaryotes, the reaction is carried out by a hexameric enzyme, activated by GTP and inhibited by UTP. In the present study, Streptococcus pneumoniae UMP kinase was studied as a target for antibacterial research and its interest was confirmed by the demonstration of the essentiality of the gene for cell growth. In the presence of MnCl2 or MgCl2, the saturation kinetics of recombinant purified UMP kinase was hyperbolic for UMP (Km=0.1 mM) and sigmoidal for ATP (the substrate concentration at half-saturation S0.5=9.4±0.7 mM and n=1.9±0.1 in the presence of MgCl2). GTP increased the affinity for ATP and decreased the Hill coefficient (n). UTP decreased the affinity for ATP and only slightly increased the Hill coefficient. The kcat (175±13 s−1 in the presence of MgCl2) was not affected by the addition of GTP or UTP, whose binding site was shown to be different from the active site. The hydrodynamic radius of the protein similarly decreased in the presence of ATP or GTP. There was a shift in the pH dependence of the activity when the ATP concentration was switched from low to high. These results support the hypothesis of an allosteric transition from a conformation with low affinity for ATP to a form with high affinity, which would be induced by the presence of ATP or GTP. PMID:15324307

  18. Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis.

    PubMed

    Carroll, Bernadette; Korolchuk, Viktor I; Sarkar, Sovan

    2015-10-01

    Maintenance of amino acid homeostasis is important for healthy cellular function, metabolism and growth. Intracellular amino acid concentrations are dynamic; the high demand for protein synthesis must be met with constant dietary intake, followed by cellular influx, utilization and recycling of nutrients. Autophagy is a catabolic process via which superfluous or damaged proteins and organelles are delivered to the lysosome and degraded to release free amino acids into the cytoplasm. Furthermore, autophagy is specifically activated in response to amino acid starvation via two key signaling cascades: the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and the general control nonderepressible 2 (GCN2) pathways. These pathways are key regulators of the integration between anabolic (amino acid depleting) and catabolic (such as autophagy which is amino acid replenishing) processes to ensure intracellular amino acid homeostasis. Here, we discuss the key roles that amino acids, along with energy (ATP, glucose) and oxygen, are playing in cellular growth and proliferation. We further explore how sophisticated methods are employed by cells to sense intracellular amino acid concentrations, how amino acids can act as a switch to dictate the temporal and spatial activation of anabolic and catabolic processes and how autophagy contributes to the replenishment of free amino acids, all to ensure cell survival. Relevance of these molecular processes to cellular and organismal physiology and pathology is also discussed. PMID:24965527

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

    PubMed

    Nielsen, Christian F; Huttner, Diana; Bizard, Anna H; Hirano, Seiki; Li, Tian-Neng; Palmai-Pallag, Timea; Bjerregaard, Victoria A; Liu, Ying; Nigg, Erich A; Wang, Lily Hui-Ching; Hickson, Ian D

    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 abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH(-/-) cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH(-/-) cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis. PMID:26643143

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

    PubMed Central

    Nielsen, Christian F.; Huttner, Diana; Bizard, Anna H.; Hirano, Seiki; Li, Tian-Neng; Palmai-Pallag, Timea; Bjerregaard, Victoria A.; Liu, Ying; Nigg, Erich A.; Wang, Lily Hui-Ching; Hickson, Ian D.

    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 abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH−/− cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH−/− cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis. PMID:26643143

  1. Brain activity elicited by positive and negative feedback in preschool-aged children.

    PubMed

    Mai, Xiaoqin; Tardif, Twila; Doan, Stacey N; Liu, Chao; Gehring, William J; Luo, Yue-Jia

    2011-01-01

    To investigate the processing of positive vs. negative feedback in children aged 4-5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN) elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW) over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period. PMID:21526189

  2. Brain Activity Elicited by Positive and Negative Feedback in Preschool-Aged Children

    PubMed Central

    Mai, Xiaoqin; Tardif, Twila; Doan, Stacey N.; Liu, Chao; Gehring, William J.; Luo, Yue-Jia

    2011-01-01

    To investigate the processing of positive vs. negative feedback in children aged 4–5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN) elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW) over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period. PMID:21526189

  3. Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery

    PubMed Central

    Ammendola, Michele; Sacco, Rosario; Sammarco, Giuseppe; Piardi, Tullio; Zuccalà, Valeria; Patruno, Rosa; Zullo, Alessandra; Zizzo, Nicola; Nardo, Bruno; Marech, Ilaria; Crovace, Alberto; Gadaleta, Cosmo Damiano; Pessaux, Patrick; Ranieri, Girolamo

    2016-01-01

    Background Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase phosphorylation. Nevertheless, no data are available concerning the relationship between MC density positive to tryptase (MCDPT), endothelial cells positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the main clinicopathological features, in early HCC patients who underwent surgery. Methods A series of 53 HCC patients with early stage (stage 0 according to the Barcelona Clinic Liver Cancer Staging Classification) were selected and then underwent surgery. Tumor tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR-2-MVD, and C-MVD. Results A significant correlation between MCDPT, PAR-2-MVD, and C-MVD groups, each correlated to the others, was found by Pearson t-test analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other significant correlation was found. Conclusion Our in vivo pilot data suggest that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further evaluated as a target of antiangiogenic therapy. PMID:27499640

  4. Cleavages and co-operation in the UK alcohol industry: A qualitative study

    PubMed Central

    2012-01-01

    sectors, but within them. Cleavages were evident within the producer sector between different product categories and within the retail sector between different types of off-trade retailers. However, trade associations were particularly important in providing a means by which the entire industry, or broad sectors within it, could speak with a single voice, despite the limitations on this. There was also evidence of ad-hoc cooperation on specific issues, which resulted from both formal and informal contacts between industry actors. Conclusions Alcohol industry corporations and trade associations collaborate with one another effectively where there are shared interests, allowing the best placed bodies to lead on a given issue. Thus, whilst industry actors may be deeply divided on certain issues they are able to coordinate their positions on occasions where there are clear advantages in so doing. Health policymakers may benefit from an awareness of the multiplicity of interests within the industry and the ways that these may shape collective lobbying positions. PMID:22734630

  5. Photogrammetric and Global Positioning System Measurements of Active Pahoehoe Lava Lobe Emplacement on Kilauea, Hawaii

    NASA Technical Reports Server (NTRS)

    Hamilton, Christopher W.; Glaze, Lori S.; James, Mike R.; Baloga, Stephen M.; Fagents, Sarah A.

    2012-01-01

    Basalt is the most common rock type on the surface of terrestrial bodies throughout the solar system and -- by total volume and areal coverage -- pahoehoe flows are the most abundant form of basaltic lava in subaerial and submarine environments on Earth. A detailed understanding of pahoehoe emplacement processes is necessary for developing accurate models of flow field development, assessing hazards associated with active lava flows, and interpreting the significance of lava flow morphology on Earth and other planetary bodies. Here, we examine the active emplacement of pahoehoe lobes along the margins of the Hook Flow from Pu'u 'O'o on Kilauea, Hawaii. Topographic data were acquired between 21 and 23 February 2006 using stereo-imaging and differential global positing system (DGPS) measurements. During this time, the average discharge rate for the Hook Flow was 0.01-0.05 cubic m/s. Using stereogrammetric point clouds and interpolated digital terrain models (DTMs), active flow fronts were digitized at 1 minute intervals. These areal spreading maps show that the lava lobe grew by a series of breakouts tha t broadly fit into two categories: narrow (0.2-0.6 m-wide) toes that grew preferentially down-slope, and broad (1.4-3.5 m-wide) breakouts that formed along the sides of the lobe, nearly perpendicular to the down-flow axis. These lobes inflated to half of their final thickness within approx 5 minutes, with a rate of inflation that generally deceased with time. Through a combination of down-slope and cross-slope breakouts, lobes developed a parabolic cross-sectional shape within tens of minutes. We also observed that while the average local discharge rate for the lobe was generally constant at 0.0064 +/- 0.0019 cubic m/s, there was a 2 to 6 fold increase in the areal coverage rate every 4.1 +/- 0.6 minutes. We attribute this periodicity to the time required for the dynamic pressurization of the liquid core of the lava lobe to exceed the cooling-induced strength of the

  6. The ACCEND program: a combined BS and MS program in environmental engineering that includes co-operative work experience.

    PubMed

    Bishop, P L; Keener, T C; Kukreti, A R; Kowel, S T

    2004-01-01

    Environmental engineering education has rapidly expanded in recent years and new teaching methods are needed. Many professionals and educators believe that a MS degree in environmental engineering should be the minimum in order to practice the profession, along with practical training. This paper describes an innovative program being offered at the University of Cincinnati that combines an integrated BS in civil engineering and an MS in environmental engineering with extensive practical co-operative education (co-op) experience, all within a five-year period. The program includes distance learning opportunities during the co-op periods. The result is a well-trained graduate who will receive higher pay and more challenging career opportunities, and who will have developed professionalism and maturity beyond that from traditional engineering programs. PMID:15193097

  7. Co-operative and frustration effects in novel perovskite-related phases

    NASA Astrophysics Data System (ADS)

    Ebbinghaus, S. G.; Riegg, S.; Götzfried, T.; Reller, A.

    2009-12-01

    We report on magnetic and electronic properties of various perovskite-type oxides containing 4d- and 5d-transition metals. The compounds under investigation crystallize in (distorted) cubic, layered, and hexagonal perovskite-related structures. These changes in structural dimensionality are reflected by different ordering phenomena. (Pseudo-) cubic perovskites ACu3B4O12 (with A = alkali, alkaline earth or rare earth; B = Ru, Ti) possess an A-site ordered structure with copper on modified A-positions. Structural investigations as well as XANES (X-ray absorption near edge structure) measurements indicate a valence degeneracy, which is keeping the oxidation state of Ru close to +4. Upon replacing Ru by Ti, the itinerant magnetism and metallic conductivity of the pure ruthenates successively change to a localized magnetic moment and a semiconducting behavior. The pure titanates like Ln2/3Cu3Ti4O12 or CaCu3Ti4O12are insulators with colossal dielectric constants. The cation-deficient Cu2+xTa4O12+δ shows a large compositional flexibility with 0.125 ≤ x ≤ 0.500. Both copper content and cooling speed have a strong impact on the crystal structure and the observed magnetic ordering. This behavior can be explained by uncompensated Cu2+-moments resulting from different site occupations. Quasi-2D La2RuO5 undergoes a structural and magnetic phase transition at roughly 160 K, leading to a diminishing magnetic moment and a semiconductor-semiconductor transition. LDA calculations reveal an antiferromagnetic coupling within pairs of neighboring Ru4+-ions, leading to a spin-Peierls like transition. New hexagonal perovskites containing Ru, Ir, and Pt crystallize in the [AO1+δ][A2BO6] structure type and contain peroxide ions (O) in the [AO1+δ] layers. La1.2Sr2.7IrO7.33 exhibits a small temperature-independent paramagnetism, which can be explained on basis of the crystal-field splitting and the strong spin-orbit coupling. The isostructural La1.2Sr2.7RuO7.33 shows a frustrated

  8. Structural requirements of position A alpha-157 in fibrinogen for the fibrin-induced rate enhancement of the activation of plasminogen by tissue-type plasminogen activator.

    PubMed Central

    Schielen, J G; Adams, H P; Voskuilen, M; Tesser, G J; Nieuwenhuizen, W

    1991-01-01

    The sequence fibrinogen-A alpha-(148-160) can mimic part of the fibrin-induced rate enhancement of the activation of plasminogen by tissue-type plasminogen activator. Previously we have reported that the lysine residue at position A alpha-157 is crucial. During our further investigations on A alpha-157 we found that lysine at position A alpha-157 may be replaced by glutamic acid. This unexpected finding prompted us to re-investigate the requirements of this position. We prepared analogues of A alpha-(148-160) in which the lysine residue at position A alpha-157 was replaced by lysine derivatives (acetyl-lysine, benzyloxycarbonyl-lysine and methanesulphonylethyloxycarbonyl-lysine), acidic residues (aspartic acid and glutamic acid), basic residues (arginine and ornithine), polar residues (glutamine and methanesulphonylethyloxycarbonylornithine), apolar residues (alanine, valine, norleucine and glutamic acid 4-nitrobenzyl ester) and glycine. These analogues were tested for their stimulatory activity. When aspartic acid, glutamic acid 4-nitrobenzyl ester or norleucine is present at position A alpha-157 in A alpha-(148-160) virtually all stimulatory capacity is lost. With valine at position A alpha-157 the stimulatory activity is marginal. None of the other replacements at position A alpha-157 caused loss of rate-enhancing properties. From these results we conclude that for the rate-enhancing effect of A alpha-(148-160) the side chain of the amino acid residue at position A alpha-157 must fulfill certain requirements: there must be one (as in alanine) or no (as in glycine) carbon atom in the side chain, or at least two carbon atoms and a polar group (charged or uncharged) to which a rather bulky group (such as the benzyloxycarbonyl group) or a polar group (such as the methanesulphonylethyloxycarbonyl group) may be attached. The highest activity [even higher than native A alpha-(148-160)] was obtained with ornithine, methanesulphonylethyloxycarbonylornithine or

  9. Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models

    PubMed Central

    2012-01-01

    Background HER2 is an oncogene, expression of which leads to poor prognosis in 30% of breast cancer patients. Although trastuzumab is apparently an effective therapy against HER2-positive tumors, its systemic toxicity and resistance in the majority of patients restricts its applicability. In this study we evaluated the effects of phenethyl isothiocyanate (PEITC) in HER2-positive breast cancer cells. Methods MDA-MB-231 and MCF-7 breast cancer cells stably transfected with HER2 (high HER2 (HH)) were used in this study. The effect of PEITC was evaluated using cytotoxicity and apoptosis assay in these syngeneic cells. Western blotting was used to delineate HER2 signaling. SCID/NOD mice were implanted with MDA-MB-231 (HH) xenografts. Results Our results show that treatment of MDA-MB-231 and MCF-7 cells with varying concentrations of PEITC for 24 h extensively reduced the survival of the cells with a 50% inhibitory concentration (IC50) of 8 μM in MDA-MB-231 and 14 μM in MCF-7 cells. PEITC treatment substantially decreased the expression of HER2, epidermal growth factor receptor (EGFR) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr-705. The expression of BCL-2-associated × (BAX) and BIM proteins were increased, whereas the levels of B cell lymphoma-extra large (BCL-XL) and X-linked inhibitor of apoptosis protein (XIAP) were significantly decreased in both the cell lines in response to PEITC treatment. Substantial cleavage of caspase 3 and poly-ADP ribose polymerase (PARP) were associated with PEITC-mediated apoptosis in MDA-MB-231 and MCF-7 cells. Notably, transient silencing of HER2 decreased and overexpressing HER2 increased the effects of PEITC. Furthermore, reactive oxygen species (ROS) generation, mitochondrial depolarization and apoptosis by PEITC treatment were much higher in breast cancer cells expressing higher levels of HER2 (HH) as compared to parent cell lines. The IC50 of PEITC following 24 h of treatment was

  10. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes

    PubMed Central

    Magnúsdóttir, Stefanía; Ravcheev, Dmitry; de Crécy-Lagard, Valérie; Thiele, Ines

    2015-01-01

    The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40–65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements. PMID:25941533

  11. A Solid Earth educational module, co-operatively developed by scientists and high school teachers through the Scripps Classroom Connection GK12 Program

    NASA Astrophysics Data System (ADS)

    Ziegler, L. B.; van Dusen, D.; Benedict, R.; Chojnacki, P. R.; Peach, C. L.; Staudigel, H.; Constable, C.; Laske, G.

    2010-12-01

    The Scripps Classroom Connection, funded through the NSF GK-12 program, pairs local high school teachers with Scripps Institution of Oceanography (SIO) graduate students in the earth and ocean sciences for their mutual professional development. An integral goal of the program is the collaborative production of quality earth science educational modules that are tested in the classroom and subsequently made freely available online for use by other educators. We present a brief overview of the program structure in place to support this goal and illustrate a module that we have developed on the Solid Earth & Plate Tectonics for a 9th grade Earth Science classroom. The unit includes 1) an exercise in constructing a geomagnetic polarity timescale which exposes students to authentic scientific data; 2) activities, labs, lectures and worksheets that support the scientific content; and 3) use of online resources such as Google Earth and interactive animations that help students better understand the concepts. The educational unit is being implemented in two separate local area high schools for Fall 2010 and we will report on our experiences. The co-operative efforts of teachers and scientists lead to educational materials which expose students to the scientific process and current science research, while teaching basic concepts using an engaging inquiry-based approach. In turn, graduate students involved gain experience communicating their science to non-science audiences.

  12. Bursts of calving activity and controls on the terminus position of Yahtse Glacier, Alaska

    NASA Astrophysics Data System (ADS)

    Bartholomaus, T. C.; Larsen, C. F.; West, M. E.; Oneel, S.

    2011-12-01

    The tidewater glacier terminus is the interface that links oceanic and glaciological processes. Tidewater glaciers contribute large amounts of cold, fresh water to their fjords. Ocean heat exerts a significant control on glacier mass balance. On the Gulf of Alaska, the terminus of tidewater Yahtse Glacier has advanced slowly since its 1990 post-Little Ice Age minimum. At Yahtse's terminus, ice flowing at 18 m/d encounters water with temperatures of up to 10.5°C (measured 1.5 km from the terminus). Profiles of temperature and salinity in Icy Bay, in which Yahtse Glacier terminates, have revealed a strongly stratified, single-cell circulation pattern. Fresh, glacier outflow exits the bay atop warm, saline Gulf of Alaska water. The Alaska Coastal Current, a major source of Icy Bay water, has warmed by 1°C over the last 40 years. These observations prompt the question of how a tidewater advance may be sustained in spite of warming ocean and atmosphere temperatures. Superimposed on Yahtse Glacier's longer-term advance have been smaller-scale summer retreats and winter-spring re-advances. These smaller fluctuations indicate that factors that change on short timescales, such as ocean conditions and weather, also have an important control on terminus position. Observed bursts in calving frequency are a further reflection of the unsteady conditions at the glacier terminus. In the present study, we use seismograms recorded on bedrock within 500 m of the glacier terminus as a calving counter. The epicenters of a significant majority of glacier-generated seismic events within the St. Elias Mountains have been located to within 15 km of the terminus of Yahtse Glacier. Previous study at Yahtse Glacier has revealed that at least 75% of these seismic events originate from calving processes, most notably through the interactions between iceberg and water. Calving frequency is characterized by a relatively steady rate of background events, punctuated by bursts of calving activity

  13. Co-Operative Advances in Behavioral Health and Performance Research and Operations

    NASA Technical Reports Server (NTRS)

    VanderArk, Stephen T.; Leveton, Lauren B.

    2011-01-01

    In organizations that engage in both operations and applied research, with operational needs guiding research questions and research informing improved operations, the ideal goal is a synergy of ideas and information. In reality, this ideal synergy is often lacking. Real-time operational needs driving day-to-day decisions, lack of communication, lag time in getting research advances plugged into operations can cause both areas to suffer from this gap between operations and research. At Johnson Space Center, the Behavior Health and Performance group (BHP) strives to bridge this gap by following a Human Research Program framework: Expectations of future operational needs identify the knowledge gaps; the gaps in turn guide research leading to a product that is transitioned into operations. Thus, the direction those of us in research take is in direct response to current and future needs of operations. Likewise, those of us in operations actively seek knowledge that is supported by evidence-based research. We make an ongoing effort to communicate across the research and operations gap by working closely with each other and making a conscious effort to keep each other informed. The objective of the proposed panel discussion is to demonstrate through the following presentations the results of a successful collaboration between research and operations and to provide ASMA members with more practical knowledge and strategies for building these bridges to serve our field of practice well. The panel will consist of six presenters from BHP operations, internal BHP research, and external research instigated by BHP who together represent the entire BHP Research Transition to Operations Framework

  14. Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.

    PubMed

    Jinzhu, Yin; Qinli, Zhang; Jin, Yang; Pan, Kang; Jianjun, Huang; Qiao, Niu

    2015-06-01

    Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 μmol/L), Al (mal)3 groups (50, 100, 400 μmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 μM BaP or 50 μM Al (mal)3 was mildly toxic, and we selected 10 μM BaP+50 μM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis. PMID:25971159

  15. Three dimensional culture of pineal cell aggregates: a model of cell-cell co-operation.

    PubMed

    Khan, N A; Shacoori, V; Havouis, R; Querné, D; Moulinoux, J P; Rault, B

    1995-05-01

    Three dimensional (3-D) cultures of pineal cell aggregates were obtained by constant gyratory shaking the heterogenous cell populations, obtained from the rat pineals, in the DMEM (Dulbecco's modified Eagle's medium). Within 4 days, the pineal cells became organized into a tissue like configuration appearing as a compact ball, evidenced by the scanning electron microscopy. The 3-D aggregates seemed to be mainly composed of pinealocytes (round-oval cells), glial (elongated cells) and other unknown cells. The heterogenous cells were separated by intercellular spaces. The ultrastructural characteristics revealed by transmission electron microscopy exhibited the presence of granular lysosomes, typical of pinealocytes actively involved in the secretion. These pineal cell aggregates secreted melatonin and other indole amines i.e. 5-methoxytryptamine (5-MT), indole acetic acid (IAA), 5-methoxy-3-indole acetic acid (5-MIAA), tryptophol (TOL) and 5-methoxytryptophol (5-MTL) in the culture medium, indicating the functional aspect of pinealocytes. The 3-D aggregates cultures had advantages over the pineal monolayer cultures as, after 4 days of culture, the amounts of indole amines secreted by 3-D aggregates were higher than those secreted by monolayer cultures. Besides, the 3-D aggregates remained functional till 24 days in the gyratory culture conditions. In the continuous perifusion system, the 3-D aggregates secreted melatonin while challanged with isoproterenol. This 3-D model of pineal cell aggregates might be useful, in future, to perform other kinetic studies of the release of indole amines in perifusion experiments as this system allows the maintenance of pineal cells for a long period of time. PMID:7550281

  16. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling.

    PubMed

    Stephen, Terri-Leigh; Higgs, Nathalie F; Sheehan, David F; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I Lorena; Kittler, Josef T

    2015-12-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function. PMID:26631479

  17. Positive affect and pain: mediators of the within-day relation linking sleep quality to activity interference in fibromyalgia.

    PubMed

    Kothari, Dhwani J; Davis, Mary C; Yeung, Ellen W; Tennen, Howard A

    2015-03-01

    Fibromyalgia (FM) is a chronic pain condition often resulting in functional impairments. Nonrestorative sleep is a prominent symptom of FM that is related to disability, but the day-to-day mechanisms relating the prior night's sleep quality to next-day reports of disability have not been examined. This study examined the within-day relations among early-morning reports of sleep quality last night, late-morning reports of pain and positive and negative affect, and end-of-day reports of activity interference. Specifically, we tested whether pain, positive affect, and negative affect mediated the association between sleep quality and subsequent activity interference. Data were drawn from electronic diary reports collected from 220 patients with FM for 21 consecutive days. The direct and mediated effects at the within-person level were estimated with multilevel structural equation modeling. Results showed that pain and positive affect mediated the relation between sleep quality and activity interference. Early-morning reports of poor sleep quality last night predicted elevated levels of pain and lower levels of positive affect at late-morning, which, in turn, predicted elevated end-of-day activity interference. Of note, positive affect was a stronger mediator than pain and negative affect was not a significant mediator. In summary, the findings identify 2 parallel mechanisms, pain and positive affect, through which the prior night's sleep quality predicts disability the next day in patients with FM. Furthermore, results highlight the potential utility of boosting positive affect after a poor night's sleep as one means of preserving daily function in FM. PMID:25679472

  18. Society of Behavioral Medicine position statement: elementary school-based physical activity supports academic achievement.

    PubMed

    Buscemi, Joanna; Kong, Angela; Fitzgibbon, Marian L; Bustamante, Eduardo E; Davis, Catherine L; Pate, Russell R; Wilson, Dawn K

    2014-12-01

    The Society of Behavioral Medicine (SBM) urges elementary schools to provide children with ample opportunities to engage in physical activity during school hours. In addition to promoting overall child health, physical activity also supports academic achievement. In addition to improving their aerobic fitness, regular physical activity improves cognitive function, influences the brain, and improves mood in children. Better aerobic fitness and physical activity are associated with increased grade point averages and standardized test scores. Despite the documented relationship between physical activity, fitness, and academic achievement, few schools have implemented physical activity as a tool to improve academic performance. SBM recommends that elementary schools provide children with the recommended 60 min of moderate-to-vigorous physical activity during school hours. Further, SBM urges schools to work with the local school districts and state education departments to mandate minimum physical activity time for elementary school physical education. PMID:25584093

  19. Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms

    PubMed Central

    Erkelenz, Steffen; Mueller, William F.; Evans, Melanie S.; Busch, Anke; Schöneweis, Katrin; Hertel, Klemens J.; Schaal, Heiner

    2013-01-01

    Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5′ splice sites. SR proteins enhance splicing only when they are recruited to the exon. However, they interfere with splicing by simply relocating them to the opposite intronic side of the splice site. hnRNP splicing factors display analogous opposing activities, but in a reversed position dependence. Activation by SR or hnRNP proteins increases splice site recognition at the earliest steps of exon definition, whereas splicing repression promotes the assembly of nonproductive complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection. PMID:23175589

  20. Muscle Activation Differs between Three Different Knee Joint-Angle Positions during a Maximal Isometric Back Squat Exercise

    PubMed Central

    Jarbas da Silva, Josinaldo; Jon Schoenfeld, Brad; Nardi, Priscyla Silva Monteiro; Pecoraro, Silvio Luis; D'Andréa Greve, Julia Maria; Hartigan, Erin

    2016-01-01

    The purpose of this study was to compare muscle activation of the lower limb muscles when performing a maximal isometric back squat exercise over three different positions. Fifteen young, healthy, resistance-trained men performed an isometric back squat at three knee joint angles (20°, 90°, and 140°) in a randomized, counterbalanced fashion. Surface electromyography was used to measure muscle activation of the vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), biceps femoris (BF), semitendinosus (ST), and gluteus maximus (GM). In general, muscle activity was the highest at 90° for the three quadriceps muscles, yet differences in muscle activation between knee angles were muscle specific. Activity of the GM was significantly greater at 20° and 90° compared to 140°. The BF and ST displayed similar activation at all joint angles. In conclusion, knee position alters muscles activation of the quadriceps and gluteus maximus muscles. An isometric back squat at 90° generates the highest overall muscle activation, yet an isometric back squat at 140° generates the lowest overall muscle activation of the VL and GM only. PMID:27504484

  1. Decision making and co-operation between stakeholders within the process of sick leave. A case study in a Danish municipality.

    PubMed

    Johansen, Kristina; Andersen, John Sahl; Mikkelsen, Sigurd; Lynge, Elsebeth

    2011-01-01

    The study addresses how recent reforms of the Sickness Benefit Act in Denmark are put into practice. A single case study embedded with five subunits of analysis based on "real life" cases has been conducted in a Danish municipality. Five "sick-listed" citizens and their respective municipal case manager and general practitioner (GP) were interviewed. Two key persons within the municipality were interviewed as background informants. The GPs and case managers ability to co-operate was hampered by lack of time, frequent staff turnover, lack of financial resources, and low accessibility. The motivation for co-operation was low due to low status of social medical issues, lack of feedback and lack of trust. The co-operation was characterized by sequential task integration. The stakeholders encountered difficulties when reciprocal task integration was needed. The decision making was affected by legal constraints and conflicting paradigms of key stakeholders. Rather than forcing co-operation, policymakers should increase the stakeholders' abilities and improve the conditions that create the low level of trust and hamper the willingness to co-operate. PMID:20795840

  2. Process evaluation of "Girls on the Run": exploring implementation in a physical activity-based positive youth development program.

    PubMed

    Iachini, Aidyn L; Beets, Michael W; Ball, Annahita; Lohman, Mary

    2014-10-01

    Many positive youth development programs rely on physical activity as a primary program component. Referred to as physical activity-based youth development programs, these program designs have great potential for promoting healthy youth development. This study examined how one such physical activity-based positive youth development program was implemented in order to identify design features critical to maximizing positive youth outcomes. This mixed method, multi-site process evaluation of Girls on the Run (GOTR) utilized focus groups, site visits, and self-report implementation checklists. Implementation scores were calculated to assess implementation fidelity across twenty-nine sites, and qualitative data were inductively analyzed to identify factors influential for implementation. Results reveal variability in how GOTR was implemented. Five themes emerged from the data that represented factors serving as facilitators or barriers to programmatic implementation. These included contextual/environmental factors (e.g., parental involvement, relationships with school personnel), organizational factors (e.g., implementation support and responsiveness of staff), program-specific factors (e.g., curriculum design), coach factors (e.g., existing relationships with participants, responsiveness to participant's needs), and youth factors (e.g., behavioral and discipline issues). Study findings have implications for improving the design of physical activity-based and other positive youth development programs, with relevance to evaluators, program planners, youth development leaders, and others working with children and youth. PMID:24858574

  3. INITIATION/PROMOTION BIOASSAY IN RAT LIVER: USE OF GAMMA GLUTAMYLTRANSPEPTIDASE-POSITIVE FOCI TO INDICATE CARCINOGENIC ACTIVITY

    EPA Science Inventory

    Gamma Glutamyltranspeptidase (GGTase)-positive foci have been used to indicate activity in an initiation/promotion bioassay in rat liver. This rat liver foci bioassay has been proposed for inclusion in tier 2 of a three tier decision tree approach to carcinogenesis testing where ...

  4. Common origin of positive ionospheric storms at middle latitudes and the geomagnetic activity effect at low latitudes

    SciTech Connect

    Proelss, G.W. )

    1993-04-01

    The author looks for a correlation between two different atmospheric effects. They are a positive atmospheric storm (an anomalous increase in the F2 region ionization density), observed at middle latitudes, and the geomagnetic activity effect (the anomalous changes of temperature and gas density seen in the thermosphere), observed at low latitudes. A temporal correlation is sought to test the argument that both of these effects are the result of travelling atmospheric disturbances (TAD). A TAD is a pulselike atmospheric wave thought to be generated by substorm activity, and to propagate with high velocity (600 m/s) from polar latitudes toward equatorial latitudes. The author looks at data from five separate events correlating magnetic, ionospheric, and neutral atmospheric measurements. The conclusion is that there is a positive correlation between magnetic substorm activity at high latitudes, and positive ionospheric storms at middle latitudes and geomagnetic activity at low latitudes. The time correlations are consistent with high propagation speeds between these events. The author also presents arguments which indicate that the middle latitude positive ionospheric storms are not the result of electric field effects.

  5. SUMO-activating SAE1 transcription is positively regulated by Myc

    PubMed Central

    Amente, Stefano; Lavadera, Miriam Lubrano; Palo, Giacomo Di; Majello, Barbara

    2012-01-01

    Myc protein plays a fundamental role in regulation of cell cycle, proliferation, differentiation and apoptosis by modulating the expression of a large number of targets. Here we report the transactivation ability of the human Myc protein to activate the SUMO-activating enzyme SAE1 transcription. We found that Myc activates SAE1 transcription via direct binding to canonical E-Boxes sequences located close to the SAE1 transcription start site. A recent report has highlighted the crucial role of the SAE gene expression in Myc mediated oncogenesis. Our study adds new insight in this context since we show here that Myc directly activates SAE1 transcription, suggesting that Myc oncogenic activity which depends on SAE1 is ensured by Myc itself through direct binding and transcriptional activation of SAE1 expression. PMID:22679563

  6. CRP-dependent positive autoregulation and proteolytic degradation regulate competence activator Sxy of Escherichia coli.

    PubMed

    Jaskólska, Milena; Gerdes, Kenn

    2015-03-01

    Natural competence, the ability of bacteria to take up exogenous DNA and incorporate it into their chromosomes, is in most bacteria a transient phenomenon under complex genetic and environmental control. In the Gram-negative bacteria Haemophilus influenzae and Vibrio cholerae, the master regulator Sxy/TfoX controls competence development. Although not known to be naturally competent, Escherichia coli possesses a Sxy homologue and a competence regulon containing the genes required for DNA uptake. Here, we show that in contrast to other characterised Gamma-proteobacteria, E. coli Sxy is positively autoregulated at the level of transcription by a mechanism that requires cAMP receptor protein (CRP), cyclic AMP (cAMP) and a CRP-S site in the sxy promoter. Similarly, we found no evidence that Sxy expression in E. coli was regulated at the translational level. However, our analysis revealed that Sxy is an unstable protein and that its cellular level is negatively regulated at the post-translational level via degradation by Lon protease. Interestingly, in the Gram-positive model organism Bacillus subtilis, the competence master regulator ComK is also positively autoregulated at the level of transcription and negatively regulated by proteolysis. Together, these findings reveal striking similarities between the competence regulons of a Gram-positive and a Gram-negative bacterium. PMID:25491382

  7. Rewards for Kids! Ready-to-Use Charts and Activities for Positive Parenting.

    ERIC Educational Resources Information Center

    Shiller, Viriginia M.; Schneider, Meg F.

    Finding ways to encourage preschoolers and elementary school children to behave well without resorting to scolding, threats, or bribery is a challenge for parents. This book advocates the positive parenting technique of rewards as the key to good behavior and shows parents how to use a variety of child-friendly sticker charts and other tools to…

  8. Empathy Is Associated with Dynamic Change in Prefrontal Brain Electrical Activity during Positive Emotion in Children

    ERIC Educational Resources Information Center

    Light, Sharee N.; Coan, James A.; Zahn-Waxler, Carolyn; Frye, Corrina; Goldsmith, H. Hill; Davidson, Richard J.

    2009-01-01

    Empathy is the combined ability to interpret the emotional states of others and experience resultant, related emotions. The relation between prefrontal electroencephalographic asymmetry and emotion in children is well known. The association between positive emotion (assessed via parent report), empathy (measured via observation), and…

  9. Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia.

    PubMed

    Hooker, Christine I; Benson, Taylor L; Gyurak, Anett; Yin, Hong; Tully, Laura M; Lincoln, Sarah Hope

    2014-02-01

    Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia. PMID:24661170

  10. The Positive Effect on Determinants of Physical Activity of a Tailored, General Practice-Based Physical Activity Intervention

    ERIC Educational Resources Information Center

    Van Sluijs, E. M. F.; Van Poppel, M. N. M.; Twisk, J. W. R.; Brug, J.; Van Mechelen, W.

    2005-01-01

    PACE (Physician-based Assessment and Counseling for Exercise) is an individualized theory-based minimal intervention strategy aimed at the enhancement of regular physical activity. The aim of this study was to evaluate the effectiveness of a PACE intervention applied by general practitioners (GPs) on potential determinants of physical activity. A…

  11. Positionality and Active Learning: Confronting Privilege in Field-Exercise Design

    ERIC Educational Resources Information Center

    Hankins, Katherine B.; Yarbrough, Robert A.

    2008-01-01

    University instructors are increasingly drawing on active learning exercises to engender critical thinking skills among students. In this article, we introduce the design and implementation of an active learning exercise about mobility and transportation that we assigned in an introductory human geography class at the University of Georgia. The…

  12. Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions

    NASA Astrophysics Data System (ADS)

    Das, Jayajit

    2013-01-01

    How do single cell fate decisions induced by activation of key signaling proteins above threshold concentrations within a time interval are affected by stochastic fluctuations in biochemical reactions? We address this question using minimal models of stochastic chemical reactions commonly found in cell signaling and gene regulatory systems. Employing exact solutions and semi-analytical methods we calculate distributions of the maximum value (N) of activated species concentrations (Pmax(N)) and the time (t) taken to reach the maximum value (Pmax(t)) within a time interval in the minimal models. We find, the presence of positive feedback interactions make Pmax(N) more spread out with a higher "peakedness" in Pmax(t). Thus positive feedback interactions may help single cells to respond sensitively to a stimulus when cell decision processes require upregulation of activated forms of key proteins to a threshold number within a time window.

  13. In Vitro Activities of a New Lipopeptide, HMR 1043, against Susceptible and Resistant Gram-Positive Isolates

    PubMed Central

    Bemer, Pascale; Juvin, Marie-Emmanuelle; Bryskier, Andre; Drugeon, Henri

    2003-01-01

    The purpose of this study was to compare the activity of HMR 1043 with those of daptomycin and teicoplanin against gram-positive isolates. Susceptibility tests were performed for 52 strains, 26 parental strains, including staphylococcal, streptococcal, enterococcal, and listerial strains, and 26 HMR 1043-resistant mutants obtained from parental strains by using the Szybalski method. Agar dilution and disk diffusion susceptibility tests were performed by the procedures outlined by the NCCLS. HMR 1043 demonstrated good activity against susceptible and resistant gram-positive bacteria. The activity of HMR 1043 in vitro was less influenced by the presence of calcium ions than that of daptomycin. Susceptibility test breakpoints were not defined because of the poor correlation coefficients obtained with the different disks tested. PMID:12937020

  14. Influence of Hamstring and Abdominal Muscle Activation on a Positive Ober's Test in People with Lumbopelvic Pain

    PubMed Central

    Tenney, H. Rich; DeBord, Aaron

    2013-01-01

    ABSTRACT Purpose: To assess the immediate effect of hamstring and abdominal activation on pain levels as measured by the Numeric Pain Scale (NPS) and hip range of motion as measured by Ober's Test in people with lumbopelvic pain. Methods: Thirteen participants with lumbopelvic pain and positive Ober's Tests completed an exercise developed by the Postural Restoration Institute™ to recruit hamstrings and abdominal muscles. Results: There was a significant increase in passive hip-adduction angles (p<0.01) and decrease in pain (p<0.01) immediately after the intervention. Conclusion: Specific exercises that activate hamstrings and abdominal muscles appear to immediately improve Ober's Test measurements and reduce pain as measured by the NPS in people with lumbo-pelvic pain. Hamstring/abdominal activation, rather than iliotibial band stretching, may be an effective intervention for addressing lumbopelvic pain and a positive Ober's Test. PMID:24381375

  15. Physical activity, sleep, and C-reactive protein as markers of positive health in resilient older men.

    PubMed

    Fields, Alison J; Hoyt, Robert E; Linnville, Steven E; Moore, Jeffery L

    2016-09-01

    This study explored whether physical activity and sleep, combined with the biomarker C-reactive protein, indexed positive health in older men. Many were former prisoners of war, with most remaining psychologically resilient and free of any psychiatric diagnoses. Activity and sleep were recorded through actigraphy in 120 veterans (86 resilient and 34 nonresilient) for 7 days. Resilient men had higher physical activity, significantly lower C-reactive protein levels, and 53 percent had lower cardiac-disease risk compared to nonresilient men. Sleep was adequate and not associated with C-reactive protein. Results suggest continued study is needed in actigraphy and C-reactive protein as means to index positive health. PMID:25673372

  16. Co-operation and conflict under hard and soft contracting regimes: case studies from England and Wales

    PubMed Central

    2013-01-01

    Background This paper examines NHS secondary care contracting in England and Wales in a period which saw increasing policy divergence between the two systems. At face value, England was making greater use of market levers and utilising harder-edged service contracts incorporating financial penalties and incentives, while Wales was retreating from the 1990s internal market and emphasising cooperation and flexibility in the contracting process. But there were also cross-border spill-overs involving common contracting technologies and management cultures that meant that differences in on-the-ground contracting practices might be smaller than headline policy differences suggested. Methods The nature of real-world contracting behaviour was investigated by undertaking two qualitative case studies in England and two in Wales, each based on a local purchaser/provider network. The case studies involved ethnographic observations and interviews with staff in primary care trusts (PCTs) or local health boards (LHBs), NHS or Foundation trusts, and the overseeing Strategic Health Authority or NHS Wales regional office, as well as scrutiny of relevant documents. Results Wider policy differences between the two NHS systems were reflected in differing contracting frameworks, involving regional commissioning in Wales and commissioning by either a PCT, or co-operating pair of PCTs in our English case studies, and also in different oversight arrangements by higher tiers of the service. However, long-term relationships and trust between purchasers and providers had an important role in both systems when the financial viability of organisations was at risk. In England, the study found examples where both PCTs and trusts relaxed contractual requirements to assist partners faced with deficits. In Wales, news of plans to end the purchaser/provider split meant a return to less precisely-specified block contracts and a renewed concern to build cooperation between LHB and trust staff

  17. Soil erosion increases soil microbial activity at the depositional position of eroding slopes

    NASA Astrophysics Data System (ADS)

    Meng, Xu; Cardenas, Laura M.; Donovan, Neil; Zhang, Junling; Murray, Phil; Zhang, Fusuo; Dungait, Jennifer A. J.

    2016-04-01

    Soil erosion is the most widespread form of soil degradation. Estimation of the impact of agricultural soil erosion on global carbon cycle is a topic of scientific debate, with opposing yet similar magnitude estimates of erosion as a net source or sink of atmospheric carbon. The transport and deposition of eroded agricultural soils affects not only the carbon cycle but other nutrient cycles as well. It has been estimated that erosion-induced lateral fluxes of nitrogen (N) and phosphorus (P) could be similar in magnitude to those from fertilizer application and crop removal (Quinton et al., 2010). In particular, the dynamics of soil N in eroding slopes need to be considered because the management of soil N has profound influences on the functioning of soil microorganisms, which are generally considered as the main biotic driver of soil C efflux. Carbon dioxide (CO2) emissions tend to increase in deposition positions of eroded slopes, diminishing the sink potential of eroded soils C (. As the global warming potential of nitrous oxide (N2O) is 310 times relative to that of CO2, the sink potential of agricultural erosion could easily be negated with a small increase in N2O emissions. Therefore, an investigation of the potential emissions of greenhouse gases, and especially N2O from soils affected by agricultural erosion, are required. In the present study, a field experiment was established with contrasting cultivation techniques of a C4 crop (Zea mays; δ13C = -12.2‰) to introduce 13C-enriched SOC to a soil previously cropped with C3 plants (δ13C = -29.3‰). Soils sampled from the top, middle, bottom and foot slope positions along a distinct erosion pathway were analyzed using 13C-phospholipid fatty acid (PLFA) analysis and incubated to investigate the responses of microorganisms and associated potential emissions of greenhouse gases (GHG). The total C and N contents were greatest in soils at the top slope position, whereas soil mineral N (NO3--N and NH4+-N

  18. Enhancement of figural creativity by motor activation: effects of unilateral hand contractions on creativity are moderated by positive schizotypy.

    PubMed

    Rominger, Christian; Papousek, Ilona; Fink, Andreas; Weiss, Elisabeth M

    2014-01-01

    Creativity is an important trait necessary to achieve innovations in science, economy, arts and daily life. Therefore, the enhancement of creative performance is a significant field of investigation. A recent experiment showed enhanced verbal creativity after unilateral left-hand contractions, which was attributed to elevated activation of the right hemisphere. The present study aimed to extend these findings to the domain of figural creativity. Furthermore, as creativity and positive schizotypy may share some neurobiological underpinnings associated with the right hemisphere, we studied the potential moderating effect of positive schizotypy on the effects of the experimental modification of relative hemispheric activation on creativity. In a gender-balanced sample (20 men and 20 women), squeezing a hand gripper with the left hand enhanced figural creativity on the Torrance Test of Creative Thinking compared to squeezing the gripper with the right hand. However, this was only true when positive schizotypy was low. The moderating effect of schizotypy may be produced by relatively greater activity of certain parts of the right hemisphere being a shared neuronal correlate of creativity and positive schizotypy. PMID:24266794

  19. Synthetically Tuning the 2-Position of Halogenated Quinolines: Optimizing Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive Amination Pathways.

    PubMed

    Basak, Akash; Abouelhassan, Yasmeen; Norwood, Verrill M; Bai, Fang; Nguyen, Minh Thu; Jin, Shouguang; Huigens, Robert W

    2016-06-27

    Agents capable of eradicating bacterial biofilms are of great importance to human health as biofilm-associated infections are tolerant to our current antibiotic therapies. We have recently discovered that halogenated quinoline (HQ) small molecules are: 1) capable of eradicating methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus faecium (VRE) biofilms, and 2) synthetic tuning of the 2-position of the HQ scaffold has a significant impact on antibacterial and antibiofilm activities. Here, we report the chemical synthesis and biological evaluation of 39 HQ analogues that have a high degree of structural diversity at the 2-position. We identified diverse analogues that are alkylated and aminated at the 2-position of the HQ scaffold and demonstrate potent antibacterial (MIC≤0.39 μm) and biofilm eradication (MBEC 1.0-93.8 μm) activities against drug-resistant Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium strains while demonstrating <5 % haemolysis activity against human red blood cells (RBCs) at 200 μm. In addition, these HQs demonstrated low cytotoxicity against HeLa cells. Halogenated quinolines are a promising class of antibiofilm agents against Gram-positive pathogens that could lead to useful treatments against persistent bacterial infections. PMID:27245927

  20. A novel temozolomide analog, NEO212, with enhanced activity against MGMT-positive melanoma in vitro and in vivo.

    PubMed

    Chen, Thomas C; Cho, Hee-Yeon; Wang, Weijun; Nguyen, Jenny; Jhaveri, Niyati; Rosenstein-Sisson, Rachel; Hofman, Florence M; Schönthal, Axel H

    2015-03-28

    The alkylating agent temozolomide (TMZ) represents an important component of current melanoma therapy, but overexpression of O6-methyl-guanine DNA methyltransferase (MGMT) in tumor cells confers resistance to TMZ and impairs therapeutic outcome. We investigated a novel perillyl alcohol (POH)-conjugated analog of TMZ, NEO212, for its ability to exert anticancer activity against MGMT-positive melanoma cells. Human melanoma cells with variable MGMT expression levels were treated with NEO212, TMZ, or perillyl alcohol in vitro and in vivo, and markers of DNA damage and apoptosis, and tumor cell growth were investigated. NEO212 displayed substantially greater anticancer activity than any of the other treatments. It reduced colony formation of MGMT-positive cells up to eight times more effectively than TMZ, and much more potently induced DNA damage and cell death. In a nude mouse tumor model, NEO212 showed significant activity against MGMT-positive melanoma, whereas TMZ, or a mix of TMZ plus POH, was ineffective. At the same time, NEO212 was well tolerated. NEO212 may have potential as a more effective therapy for advanced melanoma, and should become particularly suitable for the treatment of patients with MGMT-positive tumors. PMID:25524552

  1. The Physiologic and Behavioral Implications of Playing Active and Sedentary Video Games in a Seated and Standing Position

    PubMed Central

    SANDERS, GABRIEL J.; REBOLD, MICHAEL; PEACOCK, COREY A.; WILLIAMSON, MEAGAN L.; SANTO, ANTONIO S.; BARKLEY, JACOB E.

    2014-01-01

    Previous studies have assessed physiologic response while playing video games per manufacturer instructions with participants standing during active video game play and seated during sedentary game play. It is not known whether an assigned seated or standing position affects positional preference and oxygen consumption (VO2) while gaming. The purpose of the study was to assess VO2 and preference of playing active and sedentary video games in a seated and standing position. VO2 was assessed in 25 participants during four, 20-minute conditions; resting, PlayStation 2 Madden NFL Football 2011, Nintendo Wii-Sports Boxing and Nintendo Wii Madden NFL Football 2011. Each condition was divided into two positional conditions (10 minutes seated, 10 minutes standing) and each participant indicated their positional preference after each 20-minute condition. Standing VO2 (4.4 ± 0.2 ml • kg−1 • min−1 PS2, 4.6 ± 0.1 ml • kg−1 • min−1 Wii Madden, 6.8 ± 0.3 ml • kg−1 • min−1Wii Boxing) was significantly (p ≤ 0.001) greater than seated VO2 (4.0 ± 0.1 ml • kg−1 • min−1 PS2, 4.2 ± 0.1 ml • kg−1 • min−1 Wii Madden, 6.1 ± 0.3 ml • kg−1 • min−1Wii Boxing) for each gaming condition. Participants preferred (p ≤ 0.001) to sit for all gaming conditions except Wii Boxing. Playing video games while standing increases VO2 to a greater extent than playing the same games in a seated position. Standing was only preferred for the most physiologically challenging game, Wii Boxing. Gaming position should be considered when assessing the physiologic and behavioral outcomes of playing video games.

  2. Potential long-acting anticonvulsants. 1; Synthesis and activity of succinimides containing an alkylating group at the 2 position.

    PubMed

    Kornet, M J; Crider, A M; Magarian, E O

    1977-03-01

    The synthesis of succinimide derivatives in which alkylating groups have been attached to the 2 positions of the ring or to the para position of the 2-phenyl substituent is described. The alkylating groups used were (a) alpha-haloacetyl, (b) alpha-haloacetamido, (c) maleimido, and (d) maleamyl. These compounds were prepared as potential long-acting anticonvulsants. Several of these derivatives exhibited activity against metrazole-induced seizures comparable to phensuximde, The maleimide 16 and the bromoacetamido derivative 23 exhibited a duration of action of at least 3.5 h. PMID:845873

  3. Local RhoA activation induces cytokinetic furrows independent of spindle position and cell cycle stage.

    PubMed

    Wagner, Elizabeth; Glotzer, Michael

    2016-06-20

    The GTPase RhoA promotes contractile ring assembly and furrow ingression during cytokinesis. Although many factors that regulate RhoA during cytokinesis have been characterized, the spatiotemporal regulatory logic remains undefined. We have developed an optogenetic probe to gain tight spatial and temporal control of RhoA activity in mammalian cells and demonstrate that cytokinetic furrowing is primarily regulated at the level of RhoA activation. Light-mediated recruitment of a RhoGEF domain to the plasma membrane leads to rapid induction of RhoA activity, leading to assembly of cytokinetic furrows that partially ingress. Furthermore, furrow formation in response to RhoA activation is not temporally or spatially restricted. RhoA activation is sufficient to generate furrows at both the cell equator and cell poles, in both metaphase and anaphase. Remarkably, furrow formation can be initiated in rounded interphase cells, but not adherent cells. These results indicate that RhoA activation is sufficient to induce assembly of functional contractile rings and that cell rounding facilitates furrow formation. PMID:27298323

  4. Attending an activity center: positive experiences of a group of home-dwelling persons with early-stage dementia

    PubMed Central

    Söderhamn, Ulrika; Aasgaard, Live; Landmark, Bjørg

    2014-01-01

    Background In Norway, there is a focus on home-dwelling people with dementia receiving the opportunity to participate in organized meaningful activities. The aim of this study was to elucidate the experiences of home-dwelling persons with early-stage dementia who attend an activity center and participate in adapted physical and social activities delivered by nurses and volunteers. Methods The study adopted a qualitative approach, with individual interviews conducted among eight people diagnosed with early-stage dementia. The interview texts were analyzed using manifest and latent content analysis. Results Four categories, ie, “appreciated activities”, “praised nurses and volunteers”, “being more active”, and “being included in a fellowship”, as well as the overall theme “participation in appreciated activities and a sense of feeling included in a fellowship may have a positive influence on health and well-being” emerged in the analysis. The informants appreciated the adapted physical and social activities and expressed their enjoyment and gratitude. They found the physical activities useful, and they felt themselves to be included in a fellowship through cheerful nurses and volunteers. The nurses were able to create a good atmosphere and spread joy in the center together with the volunteers. The informants felt themselves valued as the persons they were. These findings indicated that such activities may have had a positive influence on the informants’ health and well-being. Conclusion In order to succeed with this kind of activity center, it is decisive that the nurses are able to tailor meaningful activities and create an environment where the persons with dementia can feel that they are respected and valued. The municipality health care service should implement such activity centers with specialist nurses in dementia care together with volunteers. PMID:25419121

  5. Joint positioning sense, perceived force level and two-point discrimination tests of young and active elderly adults

    PubMed Central

    Franco, Priscila G.; Santos, Karini B.; Rodacki, André L. F.

    2015-01-01

    Background: Changes in the proprioceptive system are associated with aging. Proprioception is important to maintaining and/or recovering balance and to reducing the risk of falls. Objective: To compare the performance of young and active elderly adults in three proprioceptive tests. Method: Twenty-one active elderly participants (66.9±5.5 years) and 21 healthy young participants (24.6±3.9 years) were evaluated in the following tests: perception of position of the ankle and hip joints, perceived force level of the ankle joint, and two-point discrimination of the sole of the foot. Results: No differences (p>0.05) were found between groups for the joint position and perceived force level. On the other hand, the elderly participants showed lower sensitivity in the two-point discrimination (higher threshold) when compared to the young participants (p < 0.01). Conclusion: Except for the cutaneous plantar sensitivity, the active elderly participants had maintained proprioception. Their physical activity status may explain similarities between groups for the joint position sense and perceived force level, however it may not be sufficient to prevent sensory degeneration with aging. PMID:26443978

  6. Introduction of Methyl Groups at C2 and C6 Positions Enhances the Antiangiogenesis Activity of Curcumin.

    PubMed

    Koo, Hyun-Jung; Shin, Sarah; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn Seong

    2015-01-01

    Curcumin has diverse biological activities, but is known to undergo rapid metabolism via reduction of vinylic double bonds and phase II conjugation. To prevent reductive metabolism of curcumin, we introduced a methyl group at both C2 and C6 positions (compound 1) or at the C2 position (compound 2) of curcumin, creating steric hindrance on double bonds against metabolizing enzymes. As predicted, these compounds were resistant to reduction by alcohol dehydrogenase. Compound 1 was further evaluated for its antiangiogenesis activity in vitro and in vivo. It exhibited significantly greater inhibitory activity than curcumin against endothelial cell migration, invasion, and tube formation. Similarly, the in vivo Matrigel plug assay in C57BL/6 mice showed more pronounced reduction of blood vessels in the plugs containing 1 than those containing curcumin. Moreover, 1 suppressed tumor growth more effectively than curcumin in a U87MG mouse xenograft model by inhibiting angiogenesis. In vivo metabolite analysis by liquid chromatography/mass spectrometry demonstrated that 1 underwent markedly slower reductive metabolism than curcumin. Taken together, our results indicate that 1 has enhanced antiangiogenesis activity and suppression of tumor growth compared with curcumin, reflecting diminished reductive metabolism owing to the introduction of methyl groups at the C2 and C6 positions of curcumin. PMID:26391485

  7. Introduction of Methyl Groups at C2 and C6 Positions Enhances the Antiangiogenesis Activity of Curcumin

    PubMed Central

    Koo, Hyun-Jung; Shin, Sarah; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn Seong

    2015-01-01

    Curcumin has diverse biological activities, but is known to undergo rapid metabolism via reduction of vinylic double bonds and phase II conjugation. To prevent reductive metabolism of curcumin, we introduced a methyl group at both C2 and C6 positions (compound 1) or at the C2 position (compound 2) of curcumin, creating steric hindrance on double bonds against metabolizing enzymes. As predicted, these compounds were resistant to reduction by alcohol dehydrogenase. Compound 1 was further evaluated for its antiangiogenesis activity in vitro and in vivo. It exhibited significantly greater inhibitory activity than curcumin against endothelial cell migration, invasion, and tube formation. Similarly, the in vivo Matrigel plug assay in C57BL/6 mice showed more pronounced reduction of blood vessels in the plugs containing 1 than those containing curcumin. Moreover, 1 suppressed tumor growth more effectively than curcumin in a U87MG mouse xenograft model by inhibiting angiogenesis. In vivo metabolite analysis by liquid chromatography/mass spectrometry demonstrated that 1 underwent markedly slower reductive metabolism than curcumin. Taken together, our results indicate that 1 has enhanced antiangiogenesis activity and suppression of tumor growth compared with curcumin, reflecting diminished reductive metabolism owing to the introduction of methyl groups at the C2 and C6 positions of curcumin. PMID:26391485

  8. The effects of core muscle activation on dynamic trunk position and knee abduction moments: implications for ACL injury.

    PubMed

    Jamison, Steve T; McNally, Michael P; Schmitt, Laura C; Chaudhari, Ajit M W

    2013-09-01

    Anterior cruciate ligament (ACL) injury is one of the most common serious lower-extremity injuries experienced by athletes participating in field and court sports and often occurs during a sudden change in direction or pivot. Both lateral trunk positioning during cutting and peak external knee abduction moments have been associated with ACL injury risk, though it is not known how core muscle activation influences these variables. In this study, the association between core muscle pre-activation and trunk position as well as the association between core muscle pre-activation and peak knee abduction moment during an unanticipated run-to-cut maneuver were investigated in 46 uninjured individuals. Average co-contraction indices and percent differences between muscle pairs were calculated prior to initial contact for internal obliques, external obliques, and L5 extensors using surface electromyography. Outside tilt of the trunk was defined as positive when the trunk was angled away from the cutting direction. No significant associations were found between pre-activations of core muscles and outside tilt of the trunk. Greater average co-contraction index of the L5 extensors was associated with greater peak knee abduction moment (p=0.0107). Increased co-contraction of the L5 extensors before foot contact could influence peak knee abduction moment by stiffening the spine, limiting sagittal plane trunk flexion (a motion pattern previously linked to ACL injury risk) and upper body kinetic energy absorption by the core during weight acceptance. PMID:23891313

  9. In Vitro Activities of Dalbavancin and Nine Comparator Agents against Anaerobic Gram-Positive Species and Corynebacteria

    PubMed Central

    Goldstein, Ellie J. C.; Citron, Diane M.; Merriam, C. Vreni; Warren, Yumi; Tyrrell, Kerin; Fernandez, Helen T.

    2003-01-01

    Dalbavancin is a novel semisynthetic glycopeptide with enhanced activity against gram-positive species. Its comparative in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method, were studied. The MICs of dalbavancin at which 90% of various isolates tested were inhibited were as follows: Actinomyces spp., 0.5 μg/ml; Clostridium clostridioforme, 8 μg/ml; C. difficile, 0.25 μg/ml; C. innocuum, 0.25 μg/ml; C. perfringens, 0.125 μg/ml; C. ramosum, 1 μg/ml; Eubacterium spp., 1 μg/ml; Lactobacillus spp., >32 μg/ml, Propionibacterium spp., 0.5 μg/ml; and Peptostreptococcus spp., 0.25 μg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains. Dalbavancin exhibited excellent activity against gram-positive strains tested and warrants clinical evaluation. PMID:12760876

  10. Mutagenic activity of halogenated propanes and propenes: effect of bromine and chlorine positioning.

    PubMed

    Låg, M; Omichinski, J G; Dybing, E; Nelson, S D; Søderlund, E J

    1994-10-01

    A series of halogenated propanes and propenes were studied for mutagenic effects in Salmonella typhimurium TA100 in the absence or presence of NADPH plus liver microsomes from phenobarbital-induced rats as an exogenous metabolism system. The cytotoxic and mutagenic effects of the halogenated propane 1,2-dibromo-3-chloropropane (DBCP) has previously been studied in our laboratories. These studies showed that metabolic activation of DBCP was required to exert its detrimental effects. All of the trihalogenated propane analogues were mutagenic when the microsomal activation system was included. The highest mutagenic activity was obtained with 1,2,3-tribromopropane, with approximately 50-fold higher activity than the least mutagenic trihalogenated propane, 1,2,3-trichloropropane. The order of mutagenicity was as follows: 1,2,3-tribromopropane > or = 1,2-dibromo- 3-chloropropane > 1,3-dibromo-2-chloropropane > or = 1,3-dichloro-2-bromopropane > 1-bromo-2,3-dichloropropane > 1,2,3-trichloropropane. Compared to DBCP, the dihalogenated propanes were substantially less mutagenic. Only 1,2-dibromopropane was mutagenic and its mutagenic potential was approximately 1/30 of that of DBCP. In contrast to DBCP, 1,2-dibromopropane showed similar mutagenic activity with and without the addition of an activation system. The halogenated propenes 2,3-dibromopropene and 2-bromo-3-chloropropene were mutagenic to the bacteria both in the absence and presence of the activation system, whereas 2,3-dichloropropene did not show any mutagenic effect. The large differences in mutagenic potential between the various halogenated propanes and propenes are proposed to be due to the formation of different possible proximate and ultimate mutagenic metabolites resulting from the microsomal metabolism of the various halogenated propanes and propenes, and to differences in the rate of formation of the metabolites. Pathways are proposed for the formation of genotoxic metabolites of di- and trihalogenated

  11. A co-operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells.

    PubMed

    Edwards, Jennifer L; Brown, Eric J; Uk-Nham, Sang; Cannon, Janne G; Blake, Milan S; Apicella, Michael A

    2002-09-01

    Little is known about the pathogenesis of gonococcal infection within the lower female genital tract. We recently described the distribution of complement receptor 3 (CR3) on epithelia of the female genital tract. Our studies further indicate that CR3-mediated endocytosis serves as a primary mechanism by which N. gonorrhoeae elicits membrane ruffling and cellular invasion of primary, human, cervical epithelial cells. We have extended these studies to describe the nature of the gonococcus-CR3 interaction. Western Blot analysis demonstrated production of alternative pathway complement components by ecto- and endocervical cells which allows C3b deposition on gonococci and its rapid conversion to iC3b. Anti-iC3b and -factor I antibodies significantly inhibited adherence and invasion of primary cervical cells, suggesting that iC3b covalently bound to the gonococcus serves as a primary ligand for CR3 adherence. However, gonococcal porin and pili also bound to the I-domain of CR3 in a non-opsonic manner. Binding of porin and pili to CR3 were required for adherence to and invasion of cervical epithelia. Collectively, these data suggest that gonococcal adherence to CR3 occurs in a co-operative manner, which requires gonococcal iC3b-opsonization, porin and pilus. In conjunction, these molecules facilitate targeting to and successful infection of the cervical epithelium. PMID:12390350

  12. Co-operative DNA binding by GAGA transcription factor requires the conserved BTB/POZ domain and reorganizes promoter topology.

    PubMed Central

    Katsani, K R; Hajibagheri, M A; Verrijzer, C P

    1999-01-01

    The POZ domain is a conserved protein-protein interaction motif present in a variety of transcription factors involved in development, chromatin remodelling and human cancers. Here, we study the role of the POZ domain of the GAGA transcription factor in promoter recognition. Natural target promoters for GAGA typically contain multiple GAGA-binding elements. Our results show that the POZ domain mediates strong co-operative binding to multiple sites but inhibits binding to single sites. Protein cross-linking and gel filtration chromatography experiments established that the POZ domain is required for GAGA oligomerization into higher order complexes. Thus, GAGA oligomerization increases binding specificity by selecting only promoters with multiple sites. Electron microscopy revealed that GAGA binds to multiple sites as a large oligomer and induces bending of the promoter DNA. Our results indicate a novel mode of DNA binding by GAGA, in which a large GAGA complex binds multiple GAGA elements that are spread out over a region of a few hundred base pairs. We suggest a model in which the promoter DNA is wrapped around a GAGA multimer in a conformation that may exclude normal nucleosome formation. PMID:9927429

  13. Influence of embedded nanocontainers on the efficiency of active anticorrosive coatings for aluminum alloys part II: influence of nanocontainer position.

    PubMed

    Borisova, Dimitriya; Möhwald, Helmuth; Shchukin, Dmitry G

    2013-01-01

    The present work contributes to the coating design of active anticorrosive coatings for the aluminum alloy, AA2024-T3. Part II is a continuation of Part I: Influence of Nanocontainer Concentration and describes further surprising aspects of the design of nanocontainer based active anticorrosive coatings, which influence their performance. The studied coating system consists of a passive sol-gel (SiO(x)/ZrO(x)) matrix and inhibitor (2-mercaptobenzothiazole) loaded mesoporous silica nanocontainers (MBT@NCs), which are dispersed only in half of the coating volume. Varying position and concentration of MBT@NCs the synergetic effect of inhibitor amount and path length on the metal surface were analyzed, considering the balance between optimum barrier properties, active protection and adhesion. The impact of MBT@NC position on passive and active corrosion resistance was investigated by electrochemical impedance spectroscopy and scanning vibrating electrode technique. Increasing the distance between MBT@NCs and metal surface led to better barrier properties but worse active corrosion inhibition. These findings improve the understanding of the factors influencing the overall performance of active anticorrosive coatings and enable the development of a coating system with optimum anticorrosion efficiency. PMID:23237235

  14. Telavancin activity tested against a contemporary collection of Gram-positive pathogens from USA Hospitals (2007-2009).

    PubMed

    Mendes, Rodrigo E; Sader, Helio S; Farrell, David J; Jones, Ronald N

    2012-01-01

    This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC(50/90), 0.12/0.25 μg/mL) was active against coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC(50/90), 0.25/0.5 μg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC(50/90), ≤ 0.25-0.5/0.5 μg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC(50/90), 0.25/0.5 μg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, ≤ 1 μg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at ≤ 1 μg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC(90), 0.06-0.12 μg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance. PMID:22078909

  15. Rational positive real approximations for LQG optimal compensators arising in active stabilization of flexible structures

    NASA Technical Reports Server (NTRS)

    Desantis, A.

    1994-01-01

    In this paper the approximation problem for a class of optimal compensators for flexible structures is considered. The particular case of a simply supported truss with an offset antenna is dealt with. The nonrational positive real optimal compensator transfer function is determined, and it is proposed that an approximation scheme based on a continued fraction expansion method be used. Comparison with the more popular modal expansion technique is performed in terms of stability margin and parameters sensitivity of the relative approximated closed loop transfer functions.

  16. Functionally Active Gap Junctions between Connexin 43-Positive Mesenchymal Stem Cells and Glioma Cells.

    PubMed

    Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Levinskii, A B; Mel'nikov, P A; Cherepanov, S A; Chekhonin, V P

    2015-05-01

    The formation of functional gap junctions between mesenchymal stem cells and cells of low-grade rat glioma C6 cells was studied in in vitro experiments. Immunocytochemical analysis with antibodies to connexin 43 extracellular loop 2 showed that mesenchymal stem cells as well as C6 glioma cells express the main astroglial gap junction protein connexin 43. Analysis of migration activity showed that mesenchymal stem cells actively migrate towards C6 glioma cells. During co-culturing, mesenchymal stem cells and glioma C6 form functionally active gap junctions mediating the transport of cytoplasmic dye from glioma cells to mesenchymal stem cells in the opposite direction. Fluorometry showed that the intensity of transport of low-molecular substances through heterologous gap junctions between mesenchymal stem cells and glioma cells is similar to that through homologous gap junctions between glioma cells. This phenomenon can be used for the development of new methods of cell therapy of high-grade gliomas. PMID:26033611

  17. Turning a Negative into a Positive: Ascending GABAergic Control of Cortical Activation and Arousal

    PubMed Central

    Brown, Ritchie E.; McKenna, James T.

    2015-01-01

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. Recent technological advances have illuminated the role of GABAergic neurons in control of cortical arousal and sleep. Sleep-promoting GABAergic neurons in the preoptic hypothalamus are well-known. Less well-appreciated are GABAergic projection neurons in the brainstem, midbrain, hypothalamus, and basal forebrain, which paradoxically promote arousal and fast electroencephalographic (EEG) rhythms. Thus, GABA is not purely a sleep-promoting neurotransmitter. GABAergic projection neurons in the brainstem nucleus incertus and ventral tegmental nucleus of Gudden promote theta (4–8 Hz) rhythms. Ventral tegmental area GABAergic neurons, neighboring midbrain dopamine neurons, project to the frontal cortex and nucleus accumbens. They discharge faster during cortical arousal and regulate reward. Thalamic reticular nucleus GABAergic neurons initiate sleep spindles in non-REM sleep. In addition, however, during wakefulness, they tonically regulate the activity of thalamocortical neurons. Other GABAergic inputs to the thalamus arising in the globus pallidus pars interna, substantia nigra pars reticulata, zona incerta, and basal forebrain regulate motor activity, arousal, attention, and sensory transmission. Several subpopulations of cortically projecting GABAergic neurons in the basal forebrain project to the thalamus and neocortex and preferentially promote cortical gamma-band (30–80 Hz) activity and wakefulness. Unlike sleep-active GABAergic neurons, these ascending GABAergic neurons are fast-firing neurons which disinhibit and synchronize the activity of their forebrain targets, promoting the fast EEG rhythms typical of conscious states. They are prominent targets of GABAergic hypnotic agents. Understanding the properties of ascending GABAergic neurons may lead to novel treatments for diseases involving disorders of cortical activation and wakefulness. PMID:26124745

  18. The effect of three different head-neck positions on the average EMG activity of three important neck muscles in the horse.

    PubMed

    Kienapfel, K

    2015-02-01

    The Knowledge of muscle activity in common head-neck positions (HNPs) is a necessary precondition for making judgements on HNPs. The aim of the study was to record the surface electromyography activities of important muscles of the horse's neck in various HNPs. The electrical activities of the m. splenius, brachiocephalicus and trapezius were recorded on both sides. Five horses, both with and without a rider, were examined in all three gaits on both hands in three different HNPs: a 'free' position, a 'gathered' (head higher, neck more flexed) position with the noseline in front of the vertical and a 'hyperflexed' position. Averages of ten consecutive gait cycles in each HNP were evaluated and compared by standard statistical methods. No difference between ridden and unridden horses could be detected. The m. brachiocephalicus was in the hyperflexed position in all gaits significantly (p < 0.01) more active than in the gathered and free position, which were not significantly different. By contrast, the m. splenius was in the hyperflexed position less active than in the free position (p < 0.02), in which it always showed the highest activity. In walking, the muscle activities in the free and gathered positions deviated significantly (p < 0.01). The m. trapezius was in the hyperflexed posture during walking significantly less active than in the free (p < 0.01) and gathered (p < 0.01) positions with the strongest activities in the free position. Again, the free and gathered positions differed significantly (p < 0.01). In trot, the same pattern occured, although the gathered and hyperflexed positions did not differ significantly. In the canter, the activities of the m. trapezius showed no differences between HNPs. In HNPs with the noseline in front of the vertical, the muscles of the topline (m. splenius, m. trapezius) are activated and trained. In the hyperflexed position, however, a major muscle of the lower topline (m. brachiocephalicus) is activated and trained. PMID

  19. Active-material additives for high-rate lead/acid batteries: have there been any positive advances?

    NASA Astrophysics Data System (ADS)

    McGregor, K.

    Low positive mass utilization poses a major problem for lead/acid batteries, particularly at high discharge rates, and is one of the major factors that limits the specific energy of the battery. The reasons for the incomplete discharge at high rates are generally ascribed to a combination of various polarization phenomena including: (i) poor acid transport from the bulk of the solution in the interior of the plate, and (ii) a continuous decrease in the conductivity of the plates due to formation of non-conductive PbSO 4. One approach to alleviating these problems is to improve the positive-plate porosity and/or conductivity by the incorporation of additives into the positive active-material. The purpose of this paper is to reew recent work with such additives, and to appraise their effectiveness towards raising battery performance.

  20. Anger is associated with reward-related electrocortical activity: Evidence from the reward positivity.

    PubMed

    Angus, Douglas J; Kemkes, Kevin; Schutter, Dennis J L G; Harmon-Jones, Eddie

    2015-10-01

    Previous research indicates that the reward positivity (RewP), an electrophysiological correlate of sensitivity and biases towards rewarding stimuli, is modulated by affective and motivational variables. Studies have provided evidence that states and traits associated with negative affect and reduced approach motivation are correlated with smaller RewP amplitudes. However, the possible confound of affective valence and motivational direction was not addressed in these studies. In the present study, we examined if anger, an emotion associated with negative affect and increased approach motivation, would affect RewP amplitude. We also investigated if RewP amplitude was related to the motivational properties of reward stimuli. One hundred male participants completed two emotion inductions intended to elicit feelings of either neutrality or anger. Each was followed by a simple gambling task, in which correct choices were followed by images of women in lingerie or swimwear. Although the RewP was elicited following each induction, there was no difference in amplitude between the neutral and anger induction. However, RewP amplitude was positively correlated with how much participants liked the reward stimuli, and this correlation was statistically larger following the anger induction. These results support a motivational interpretation for the differences in RewP amplitude reported in previous studies, suggesting that motivational direction and intensity, rather than affective valence, underlie differences in RewP amplitude. Moreover, the RewP appears to be affected by interactions between motivational state and the motivational value of reward stimuli. PMID:26084980

  1. Interactions of socioeconomic position with psychosocial and environmental correlates of children's physical activity: an observational study of South Australian families

    PubMed Central

    Dollman, James; Lewis, Nicole R

    2009-01-01

    Background Evidence for psychosocial and environmental correlates on children's physical activity is scattered and somewhat unconvincing. Further, the moderating influences of socioeconomic position (SEP) on these influences are largely unexplored. The aim of this study was to examine the interactions of SEP, operationalised by mother education, and predictors of children's physical activity based on the Youth Physical Activity Promotion Model. Methods In 2005, a sample of South Australians (10–15 y) was surveyed on psychosocial and environmental correlates of physical activity using the Children's Physical Activity Correlates Questionnaire (n = 3300) and a parent survey (n = 1720). The following constructs were derived: 'is it worth it?' (perceived outcomes); 'am I able?' (perceived competency); 'reinforcing' (parental support); and 'enabling' (parent-perceived barriers). Self-reported physical activity was represented by a global score derived from the Physical Activity Questionnaire for Adolescents. Associations among physical activity and hypothesised correlates were tested among children with mothers of high (university educated) and low (left school at or before 15 y) SEP. Results Among high SEP children, 'is it worth it?' emerged as a significant predictor of physical activity for boys and girls. Among low SEP children, 'is it worth it?' predicted boys' physical activity, while among girls, 'reinforcing' was the only significant predictor, explaining ~35% of the total explained variance in physical activity. Conclusion While perceived outcomes emerged as a consistent predictor of physical activity in this sample, parental support was a powerful limiting factor among low SEP girls. Interventions among this high risk group should focus on supporting parents to provide both emotional and instrumental support for their daughters to engage in physical activity. PMID:19678960

  2. The Impact of Family Relations on Caregivers' Positive and Negative Appraisal of Their Caretaking Activities.

    ERIC Educational Resources Information Center

    Baronet, Anne-Marie

    2003-01-01

    Examines the impact of family support and relationship difficulties between the caregiver and the care recipient on caregivers' satisfaction and subjective burden. Findings showed that relationship difficulties were associated with both satisfaction received from caregiving activities and subjective burden. Family support was not associated with…

  3. Antimicrobial activity of Enterococcus Faecium Fair-E 198 against gram-positive pathogens

    PubMed Central

    do Nascimento, Maristela da Silva; Moreno, Izildinha; Kuaye, Arnaldo Yoshiteru

    2010-01-01

    ABSTRACT This study investigated the antimicrobial activity of Enterococcus faecium FAIR-E 198 against Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. Using the critical-dilution method, the bacteriocin produced by E. faecium FAIR-E 198 inhibited all L. monocytogenes strains evaluated (1,600 to 19,200 AU mL-1). However, none of the B. cereus and S. aureus strains investigated were inhibited. The maximum activity of this bacteriocin (800 AU mL-1) was observed in MRS broth, while the activity in milk was 100 AU mL-1. In the co-cultivation test in milk, B. cereus K1-B041 was reduced to below the detection limit (1.00 log CFU mL-1) after 48 h. E. faecium reduced the initial L. monocytogenes Scott A population by 1 log CFU mL-1 after 3 h at 35°C, However, the pathogen regained growth, reaching 3.68 log CFU mL-1 after 48 h. E. faecium did not influence the growth of S. aureus ATCC 27154 during the 48 h of co-cultivation, Therefore, it can be concluded that the effectiveness of the antimicrobial activity of E. faecium FAIR-E 198 is strictly related to the species and strain of the target microorganism and to the culture medium, PMID:24031466

  4. Development of Positive Racial Attitudes, Knowledges, and Activities in Pre-Service Social Studies Teachers.

    ERIC Educational Resources Information Center

    Swick, Kevin J.; Lamb, Morris L.

    Information on aspects of social studies teachers' racial attitudes, knowledges, and skill in implementing relevant ethnic-racial activities in the classroom are presented. Major research studies that have examined teacher attitudes toward black and other minority group children are discussed along with information on programs that have attempted…

  5. An Activity Theory Analysis of Teaching Goals versus Student Epistemological Positions

    ERIC Educational Resources Information Center

    Jaworski, Barbara; Robinson, Carol; Matthews, Janette; Croft, Tony

    2012-01-01

    A teaching innovation for first year engineering students' was designed to involve inquiry-based questions, an electronic graphical medium, small group activity and modifications to assessment. The use of an inquiry approach was intended to encourage students' deeper engagement with mathematics and more conceptual understanding. Data were…

  6. Pavlov's Position on Old Age within the Framework of the Theory of Higher Nervous Activity.

    ERIC Educational Resources Information Center

    Windholz, George

    1995-01-01

    In later life, I. P. Pavlov incorporated his findings on aging into his theory of higher nervous activity. Some of the major findings showed that salivary conditioning and stimulus differentiation were difficult to establish in old dogs, but that conditioned reflexes established earlier in life persisted into old age. Pavlov hypothesized that…

  7. Graduated Exposure and Positive Reinforcement to Overcome Setting and Activity Avoidance in an Adolescent with Autism

    ERIC Educational Resources Information Center

    Schmidt, Jonathan D.; Luiselli, James K.; Rue, Hanna; Whalley, Katherine

    2013-01-01

    Some students who have developmental disabilities avoid settings and activities that can improve their learning and quality of life. This two-phase study concerned an adolescent boy with autism who avoided the gross-motor exercise room, gymnasium, and music room at his school; he demonstrated distress, agitation, and problem behaviors when…

  8. Multiple Intelligences and Positive Life Habits: 174 Activities for Applying Them in Your Classroom.

    ERIC Educational Resources Information Center

    Beachner, Lynne; Pickett, Anola

    This book offers teachers a toolbox for discovering the innate strengths and talents and the unique learning styles of each student. Drawing from Howard Gardner's work on multiple intelligences, the book offers more than a dozen activities specifically tailored to each of the eight multiple intelligences: verbal/linguistic, mathematical/logical,…

  9. The Effects of Aesthetic Science Activities on Improving At-Risk Families Children's Anxiety About Learning Science and Positive Thinking

    NASA Astrophysics Data System (ADS)

    Hong, Zuway-R.; Lin, Huann-shyang; Chen, Hsiang-Ting; Wang, Hsin-Hui; Lin, Chia-Jung

    2014-01-01

    The purpose of this study was to explore the effects of aesthetic science activities on improving elementary school at-risk families' children's positive thinking, attitudes toward science, and decreasing their anxiety about learning science. Thirty-six 4th-grade children from at-risk families volunteered to participate in a 12-week intervention and formed the experimental group; another 97 typical 4th graders were randomly selected to participant in the assessment and were used as the comparison group. The treatment for experimental group children emphasized scaffolding aesthetic science activities and inquiry strategies. The Elementary School Student Questionnaire was administered to assess all children's positive thinking, attitudes toward science, and anxiety about learning science. In addition, nine target children from the experimental group with the lowest scores on either positive thinking, or attitudes toward science, or with the highest scores on anxiety about learning science in the pre-test were recruited to be interviewed at the end of the intervention and observed weekly. Confirmatory factor analyses, analyses of covariance, and content theme analysis assessed the similarities and differences between groups. It was found that the at-risk families' children were motivated by the treatment and made significant progress on positive thinking and attitudes toward science, and also decreased their anxiety about learning science. The findings from interviews and classroom observations also revealed that the intervention made differences in children's affective perceptions of learning science. Implication and research recommendation are discussed.

  10. The anti-HER3 antibody in combination with trastuzumab exerts synergistic antitumor activity in HER2-positive gastric cancer.

    PubMed

    Wang, Qiwei; Zhang, Xiaotian; Shen, Enyun; Gao, Jing; Cao, Fengqi; Wang, Xiaojuan; Li, Yilin; Tian, Tiantian; Wang, Jingyuan; Chen, Zuhua; Wang, Jiayuan; Shen, Lin

    2016-09-28

    The anti-HER2 monoclonal antibody trastuzumab is central to the treatment of HER2-positive gastric cancer (GC); however, its responses are limited. HER3 seems to be the preferred dimerization partner with HER2 and is emerging as a key target for complete blockade of downstream pathways and better clinical response. In this study, we report that novel anti-HER3 antibodies (1A5-3D4) that can neutralize multiple modes of HER3 activation, combined with trastuzumab, exhibited synergistic inhibitory effect on the cell proliferation in HER2-positive GC cell lines. Follow-up studies revealed that the combination treatment significantly inhibited phosphorylation of HER3 as well as AKT and ERK signals. In vivo experiments further showed that the anti-tumor effect of trastuzumab was enhanced by its combination with 1A5-3D4 in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. 1A5-3D4 in combination with trastuzumab exhibits a synergistic inhibitory effect on tumor activity, suggesting that targeting both HER2 and HER3 resulted in an improved treatment effects on HER2-positive GC. PMID:27317872

  11. Antibacterial activity of grape extracts on cagA-positive and -negative Helicobacter pylori clinical isolates.

    PubMed

    Martini, S; D'Addario, C; Braconi, D; Bernardini, G; Salvini, L; Bonechi, C; Figura, N; Santucci, A; Rossi, C

    2009-11-01

    There is considerable interest in alternative/adjuvant approaches for the eradication of Helicobacter pylori using biologically active compounds, especially antioxidants from plants. In the present work, we tested the antioxidant and antimicrobial activities of hydro-alcoholic extracts from Colorino, Sangiovese and Cabernet Sauvignon grape cultivars against H. pylori G21 (cagA-negative, cagA-) and 10K, (cagApositive, cagA+) clinical isolates. We determined the minimum bactericidal concentration (MBC) by incubating strain suspensions in Brucella broth with fetal bovine serum and samples at different concentrations in a final volume of 100 microl in a microaerobic atmosphere. After incubation, subcultures were carried out on Brucella agar plates which were incubated for 3-5 days in a microaerobic environment. The lowest concentration in broth, where the subculture on agar showed complete absence of growth, was considered the MBC.The Colorino extract showed the highest antibacterial activity against G21 strain (MBC=1.35 mg/ml), while Sangiovese and Carbernet MBCs were 4.0 mg/ml ca. H. pylori 10K was only susceptible to Colorino after 48 hours (MBC = 3.57 mg/ml). Resveratrol exhibited the highest antibacterial activity. interestingly, the most pathogenic strain (10K) was less susceptible to both the grape extracts and the isolated compounds. These results suggest that the administration of grape extracts and wine constituents, in addition to antibiotics, might be useful in the treatment of H. pylori infection. Should the reduced susceptibility of 10K strain be extended to all the cagA+ H. pylori isolates, which are endowed with cancer promoter activity, this observation may help explain why the organisms expressing CagA are more closely associated with atrophic gastritis and gastric carcinoma development. PMID:19933041

  12. Performance Analysis of Positive-feedback-based Active Anti-islanding Schemes for Inverter-Based Distributed Generators

    SciTech Connect

    Du, Pengwei; Aponte, Erick E.; Nelson, J. Keith

    2010-06-14

    Recently proposed positive-feedback-based anti-islanding schemes (AI) are highly effective in preventing islanding without causing any degradation in power quality. This paper aims to analyze the performance of these schemes quantitatively in the context of the dynamic models of inverter-based distributed generators (DG). In this study, the characteristics of these active anti-islanding methods are discussed and design guidelines are derived.

  13. Functionally active ganglioneuroma with increased plasma and urinary catecholamines and positive iodine 131-meta-iodobenzylguanidine scintigraphy

    SciTech Connect

    Clerico, A.; Jenkner, A.; Castello, M.A.; Ciofetta, G.; Lucarelli, C.; Codini, M. )

    1991-01-01

    Ganglioneuromas are usually considered not to be functionally active. Studies of their catecholamine excretory pattern and of their imaging by means of the adrenergic tracing agent 131-I-MIBG have been therefore sparse. We report on a case of secretory ganglioneuroma, as demonstrated by the increased urinary excretion of the catecholamine metabolites HVA and VMA, increased plasma dopamine and epinephrine levels, and positive 131-I-MIBG scintigraphy. We must therefore be aware that a functionally active tumor is not necessarily a neuroblastoma, and that the diagnosis should be biopsy proven.

  14. Isolation of Highly Active Monoclonal Antibodies against Multiresistant Gram-Positive Bacteria

    PubMed Central

    Rossmann, Friederike S.; Laverde, Diana; Kropec, Andrea; Romero-Saavedra, Felipe; Meyer-Buehn, Melanie; Huebner, Johannes

    2015-01-01

    Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics. Staphylococci and enterococci are the predominant Gram-positive species associated with hospital-acquired infections. These infections often lead to extended hospital stay and excess mortality. In this study, a panel of fully human monoclonal antibodies was isolated from a healthy individual by selection of B-cells producing antibodies with high opsonic killing against E. faecalis 12030. Variable domains (VH and VL) of these immunoglobulin genes were amplified by PCR and cloned into an eukaryotic expression vector containing the constant domains of a human IgG1 molecule and the human lambda constant domain. These constructs were transfected into CHO cells and culture supernatants were collected and tested by opsonophagocytic assay against E. faecalis and S. aureus strains (including MRSA). At concentrations of 600 pg/ml, opsonic killing was between 40% and 70% against all strains tested. Monoclonal antibodies were also evaluated in a mouse sepsis model (using S. aureus LAC and E. faecium), a mouse peritonitis model (using S. aureus Newman and LAC) and a rat endocarditis model (using E. faecalis 12030) and were shown to provide protection in all models at a concentration of 4 μg/kg per animal. Here we present a method to produce fully human IgG1 monoclonal antibodies that are opsonic in vitro and protective in vivo against several multiresistant Gram-positive bacteria. The monoclonal antibodies presented in this study are significantly more effective compared to another monoclonal antibody currently in clinical trials. PMID:25706415

  15. Individual Differences in Anticipatory Somatosensory Cortex Activity for Shock is Positively Related with Trait Anxiety and Multisensory Integration

    PubMed Central

    Greening, Steven G.; Lee, Tae-Ho; Mather, Mara

    2016-01-01

    Anxiety is associated with an exaggerated expectancy of harm, including overestimation of how likely a conditioned stimulus (CS+) predicts a harmful unconditioned stimulus (US). In the current study we tested whether anxiety-associated expectancy of harm increases primary sensory cortex (S1) activity on non-reinforced (i.e., no shock) CS+ trials. Twenty healthy volunteers completed a differential-tone trace conditioning task while undergoing fMRI, with shock delivered to the left hand. We found a positive correlation between trait anxiety and activity in right, but not left, S1 during CS+ versus CS− conditions. Right S1 activity also correlated with individual differences in both primary auditory cortices (A1) and amygdala activity. Lastly, a seed-based functional connectivity analysis demonstrated that trial-wise S1 activity was positively correlated with regions of dorsolateral prefrontal cortex (dlPFC), suggesting that higher-order cognitive processes contribute to the anticipatory sensory reactivity. Our findings indicate that individual differences in trait anxiety relate to anticipatory reactivity for the US during associative learning. This anticipatory reactivity is also integrated along with emotion-related sensory signals into a brain network implicated in fear-conditioned responding. PMID:26751483

  16. Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double-positive thymocytes.

    PubMed

    Small, M; Kaiser, M; Tse, W; Heimfeld, S; Blumberg, S

    1996-04-01

    The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes. PMID:8625997

  17. An Engineered Cysteine-Modified Diabody For Imaging Activated Leukocyte Cell Adhesion Molecule (ALCAM)-Positive Tumors

    PubMed Central

    McCabe, Katelyn E.; Liu, Bin; Marks, James D.; Tomlinson, James S.; Wu, Hong; Wu, Anna M.

    2011-01-01

    Purpose To generate and evaluate a positron emission tomography (PET) radiotracer targeting activated leukocyte cell adhesion molecule (ALCAM/CD166). Procedures A human anti-ALCAM single chain variable fragment was reformatted to produce a covalent dimer, termed a cys-diabody (CysDb). Purified CysDb was characterized by gel electrophoresis and size exclusion chromatography, and immunoreactivity was assessed by flow cytometry and immunofluorescence. Targeting and imaging of ALCAM-positive tumors using 64Cu-DOTA-CysDb were evaluated in mice bearing human pancreatic adenocarcinoma xenografts (HPAF-II or BxPC-3). Results CysDb binds specifically to ALCAM-positive cells in vitro with an apparent affinity in the range of 1–3 nM. MicroPET images at 4 h showed specific targeting of positive tumors in vivo, a finding confirmed by biodistribution analysis, with positive-to-negative tumor ratios of 1.9±0.6 and 2.4±0.6, and positive tumor-to-blood ratios of 2.5±0.9 and 2.9±0.6 (HPAF-II and BxPC-3, respectively). Conclusions Successful imaging with 64Cu-DOTA-CysDb in animal models suggests further investigation of ALCAM as an imaging biomarker is warranted. PMID:21630083

  18. Mutual Co-operation for Schools Development: Some Experiences from Asia and the Pacific. Report of a Study Group (Bangkok, Thailand, November 6-17, 1984).

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Bangkok (Thailand). Regional Office for Education in Asia and the Pacific.

    Focusing on the use of networking structures as a means of promoting and mobilizing inter-institutional support for educational development, this publication reports on topics raised at a meeting held by the Study Group on Inter-Institutional and Other Co-operative Networking Structures. Chapter 1 reports on ways in which networking is taking root…

  19. Example of International Co-Operation in the Frame of the Project Phare (TEMPUS) in Innovations in Teaching of Environmental Hydrogeology in Engineering Education in the Czech Republic.

    ERIC Educational Resources Information Center

    Grmela, Arnost; Rapantova, Nadia

    The international TEMPUS (Trans-European Co-operating and Mobility Scheme for Higher Education between Central/Eastern Europe and European Union) project lasted from 1995-1997. In the framework of TEMPUS, a material and knowledge background was developed in order to ensure the education of the branch Geological Engineering with specialization in…

  20. Going Boldly Into the Future: A Series of Case Studies of Co-Operative Research Centres and Their Relationships with the VET Sector.

    ERIC Educational Resources Information Center

    Ferrier, Fran; Trood, Clifford; Whittingham, Karen

    This document presents case studies of 10 cooperative research centers (CRCs) across Australia and their relationships with the vocational education and training (VET) sector. The CRCs profiled in the case studies are as follows: Co-operative Research Centre for Sustainable Rice Production; Cast Alloy and Solidification Technology Co-operative…

  1. The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity

    PubMed Central

    Geng, Jing; Sun, Xiufeng; Wang, Ping; Zhang, Shihao; Wang, Xiaozhen; Wu, Hongtan; Hong, Lixin; Xie, Changchuan; Li, Xun; Zhao, Hao; Liu, Qingxu; Jiang, Mingting; Chen, Qinghua; Zhang, Jinjia; Li, Yang; Song, Siyang; Wang, Hong-Rui; Zhou, Rongbin; Johnson, Randy L.; Chien, Kun-Yi; Lin, Sheng-Cai; Han, Jiahuai; Avruch, Joseph; Chen, Lanfen; Zhou, Dawang

    2015-01-01

    Summary Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit signal to recruit mitochondria remains unclear. Here, we report that the kinases Mst1 and Mst2 function to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activate Rac GTPase to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for mitochondrial recruitment to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupt the TRAF6-ECSIT complex by sequestering TRAF6, and severely dampen ROS production and greatly increase susceptibility to bacterial infection. These findings demonstrate the TLR-Mst1-Mst2-Rac signalling axis to be critical for effective phagosome-mitochondrion function and bactericidal activity. PMID:26414765

  2. Preferential Acquisition and Activation of Plasminogen Glycoform II by PAM Positive Group A Streptococcal Isolates.

    PubMed

    De Oliveira, David M P; Law, Ruby H P; Ly, Diane; Cook, Simon M; Quek, Adam J; McArthur, Jason D; Whisstock, James C; Sanderson-Smith, Martina L

    2015-06-30

    Plasminogen (Plg) circulates in the host as two predominant glycoforms. Glycoform I Plg (GI-Plg) contains glycosylation sites at Asn289 and Thr346, whereas glycoform II Plg (GII-Plg) is exclusively glycosylated at Thr346. Surface plasmon resonance experiments demonstrated that Plg binding group A streptococcal M protein (PAM) exhibits comparative equal affinity for GI- and GII-Plg in the "closed" conformation (for GII-Plg, KD = 27.4 nM; for GI-Plg, KD = 37.0 nM). When Plg was in the "open" conformation, PAM exhibited an 11-fold increase in affinity for GII-Plg (KD = 2.8 nM) compared with that for GI-Plg (KD = 33.2 nM). The interaction of PAM with Plg is believed to be mediated by lysine binding sites within kringle (KR) 2 of Plg. PAM-GI-Plg interactions were fully inhibited with 100 mM lysine analogue ε-aminocaproic acid (εACA), whereas PAM-GII-Plg interactions were shown to be weakened but not inhibited in the presence of 400 mM εACA. In contrast, binding to the KR1-3 domains of GII-Plg (angiostatin) by PAM was completely inhibited in the presence 5 mM εACA. Along with PAM, emm pattern D GAS isolates express a phenotypically distinct SK variant (type 2b SK) that requires Plg ligands such as PAM to activate Plg. Type 2b SK was able to generate an active site and activate GII-Plg at a rate significantly higher than that of GI-Plg when bound to PAM. Taken together, these data suggest that GAS selectively recruits and activates GII-Plg. Furthermore, we propose that the interaction between PAM and Plg may be partially mediated by a secondary binding site outside of KR2, affected by glycosylation at Asn289. PMID:26029848

  3. Fragmentation of positively-charged biological ions activated with a beam of high-energy cations.

    PubMed

    Chingin, Konstantin; Makarov, Alexander; Denisov, Eduard; Rebrov, Oleksii; Zubarev, Roman A

    2014-01-01

    First results are reported on the fragmentation of multiply protonated polypeptide ions produced in electrospray ionization mass spectrometry (ESI-MS) with a beam of high-energy cations as a source of activation. The ion beam is generated with a microwave plasma gun installed on a benchtop Q Exactive mass spectrometer. Precursor polypeptide ions are activated when trapped inside the collision cell of the instrument (HCD cell), and product species are detected in the Orbitrap analyzer. Upon exposure to the beam of air plasma cations (∼100 μA, 5 s), model precursor species such as multiply protonated angiotensin I and ubiquitin dissociated across a variety of pathways. Those pathways include the cleavages of C-CO, C-N as well as N-Cα backbone bonds, accordingly manifested as b/y, a, and c/z fragment ion series in tandem mass spectra. The fragmentation pattern observed includes characteristic fragments of collision-induced dissociation (CID) (b/y/a fragments) as well as electron capture/transfer dissociation (ECD, ETD) (c/z fragments), suggesting substantial contribution of both vibrational and electronic excitation in our experiments. Besides backbone cleavages, notable amounts of nondissociated precursor species were observed with reduced net charge, formed via electron or proton transfer between the colliding partners. Peaks corresponding to increased charge states of the precursor ions were also detected, which is the major distinctive feature of ion beam activation. PMID:24236851

  4. Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer.

    PubMed

    Robles, Andrew J; Cai, Shengxin; Cichewicz, Robert H; Mooberry, Susan L

    2016-06-01

    Triple-negative breast cancers (TNBC) are aggressive malignancies with no effective targeted therapies. Recent gene expression profiling of these heterogeneous cancers and the classification of cell line models now allows for the identification of compounds with selective activities against molecular subtypes of TNBC. The natural product deguelin was found to have selective activity against MDA-MB-453 and SUM-185PE cell lines, which both model the luminal androgen receptor (LAR) subtype of TNBC. Deguelin potently inhibited proliferation of these cells with GI50 values of 30 and 61 nM, in MDA-MB-453 and SUM-185PE cells, respectively. Deguelin had exceptionally high selectivity, 197 to 566-fold, for these cell lines compared to cell lines representing other TNBC subtypes. Deguelin's mechanisms of action were investigated to determine how it produced these potent and selective effects. Our results show that deguelin has dual activities, inhibiting PI3K/Akt/mTOR signaling, and decreasing androgen receptor levels and nuclear localization. Based on these data, we hypothesized that the combination of the mTOR inhibitor rapamycin and the antiandrogen enzalutamide would have efficacy in LAR models. Rapamycin and enzalutamide showed additive effects in MDA-MB-453 cells, and both drugs had potent antitumor efficacy in a LAR xenograft model. These results suggest that the combination of antiandrogens and mTOR inhibitors might be an effective strategy for the treatment of androgen receptor-expressing TNBC. PMID:27255535

  5. P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.

    PubMed

    Bompard, G; Rabeharivelo, G; Cau, J; Abrieu, A; Delsert, C; Morin, N

    2013-02-14

    The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis. Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like state. In these cells, chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed. These bipolar PAK4-depleted metaphase-like spindles have a defective astral microtubule (MT) network and are not centered in the cell but are in close contact with the cell cortex. As the metaphase-like state persists, centrosome fragmentation occurs, chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint, a phenotype that is reminiscent of cohesion fatigue. PAK4 also regulates the acto-myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest. However, we show that membrane blebs, which are strongly enriched in phospho-cofilin, are not responsible for the poor anchoring of the spindle. As PAK4 depletion interferes with the localization of components of the dynein/dynactin complexes at the kinetochores and on the astral MTs, we propose that loss of PAK4 could induce a change in the activities of motor proteins. PMID:22450748

  6. Positional error and time-activity patterns in near-highway proximity studies: an exposure misclassification analysis

    PubMed Central

    2013-01-01

    Background The growing interest in research on the health effects of near-highway air pollutants requires an assessment of potential sources of error in exposure assignment techniques that rely on residential proximity to roadways. Methods We compared the amount of positional error in the geocoding process for three different data sources (parcels, TIGER and StreetMap USA) to a “gold standard” residential geocoding process that used ortho-photos, large multi-building parcel layouts or large multi-unit building floor plans. The potential effect of positional error for each geocoding method was assessed as part of a proximity to highway epidemiological study in the Boston area, using all participants with complete address information (N = 703). Hourly time-activity data for the most recent workday/weekday and non-workday/weekend were collected to examine time spent in five different micro-environments (inside of home, outside of home, school/work, travel on highway, and other). Analysis included examination of whether time-activity patterns were differentially distributed either by proximity to highway or across demographic groups. Results Median positional error was significantly higher in street network geocoding (StreetMap USA = 23 m; TIGER = 22 m) than parcel geocoding (8 m). When restricted to multi-building parcels and large multi-unit building parcels, all three geocoding methods had substantial positional error (parcels = 24 m; StreetMap USA = 28 m; TIGER = 37 m). Street network geocoding also differentially introduced greater amounts of positional error in the proximity to highway study in the 0–50 m proximity category. Time spent inside home on workdays/weekdays differed significantly by demographic variables (age, employment status, educational attainment, income and race). Time-activity patterns were also significantly different when stratified by proximity to highway, with those participants residing in the 0–50 m

  7. Importance of the tuning of band position in optimizing the electronic coupling and photocatalytic activity of nanocomposite

    SciTech Connect

    Jin, Xiaoyan; Mok, Eun Kyung; Baek, Ji-Won; Park, Sang-Hyun; Hwang, Seong-Ju

    2015-10-15

    The electronic coupling and photocatalytic activity of Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite can be optimized by the fine-tuning of the band position of titanium oxide with nitrogen doping. The increase of the valence band energy of TiO{sub 2} by N-doping leads not only to the enhanced absorption of visible light but also to the promoted hole transfer from Ag{sub 2}CO{sub 3} to TiO{sub 2}, resulting in the efficient spatial separation of photogenerated electrons and holes. While the undoped Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite shows an inferior photocatalytic activity to the pure Ag{sub 2}CO{sub 3}, the photocatalyst performance of N-doped nanocomposite is better than those of Ag{sub 2}CO{sub 3} and undoped Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite. This observation underscores a significant enhancement of the photocatalytic activity of nanocomposite upon N-doping, a result of enhanced electronic coupling between the hybridized species. The present results clearly demonstrate the importance of the fine-tuning of band position in optimizing the photocatalytic activity of hybrid-type photocatalysts. - Highlights: • The band position of Ag{sub 2}CO{sub 3}–TiO{sub 2} can be effectively tailored by nitrogen doping. • The N-doping leads to the improvement of charge separation. • The N-doped Ag{sub 2}CO{sub 3}–TiO{sub 2} shows high photocatalytic activity.

  8. Autonomic nervous system reactivity to positive and negative mood induction: The role of acute psychological responses and frontal electrocortical activity

    PubMed Central

    Kop, Willem J.; Synowski, Stephen J.; Newell, Miranda E.; Schmidt, Louis A.; Waldstein, Shari R.; Fox, Nathan A.

    2011-01-01

    The differential effects of positive versus negative emotions on autonomic nervous system activity are insufficiently understood. This study examined the role of acute mood responses and central nervous system activity on heart rate variability (HRV) using 5-min event recall tasks (happiness and anger recall) and a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25±4 years, 55% female). HRV was measured in high frequency (HF) and low frequency (LF) domains, and frontal brain activity using electroencephalography (EEG) in the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF-HRV (p=0.005) but not HF-HRV (p=0.71). Anger Recall did not change HRV (p-values>0.10). The SCWT produced decreases in HF-HRV (p=0.001) as well as LF-HRV (p=0.001). The magnitude of feeling “happy” during Happiness Recall was positively correlated with ΔHF-HRV (p=0.050), whereas an incongruent mood state (“frustrated”) was associated with smaller ΔHF-HRV (p=0.070). Associations between frontal EEG activation and HRV responses were mostly non-significant, except for increased right frontal activation during Happiness Recall which was associated with a decrease in LF/HF ratio (p = 0.009), It is concluded that positive and negative mood induction result in differential HRV responses, which is related to both task valence and the intensity of task-induced emotions. PMID:21182891

  9. Autonomic nervous system reactivity to positive and negative mood induction: the role of acute psychological responses and frontal electrocortical activity.

    PubMed

    Kop, Willem J; Synowski, Stephen J; Newell, Miranda E; Schmidt, Louis A; Waldstein, Shari R; Fox, Nathan A

    2011-03-01

    The differential effects of positive versus negative emotions on autonomic nervous system activity are insufficiently understood. This study examined the role of acute mood responses and central nervous system activity on heart rate variability (HRV) using 5-min event recall tasks (happiness and anger recall) and a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25 ± 4 years, 55% female). HRV was measured in high frequency (HF) and low frequency (LF) domains, and frontal brain activity using electroencephalography (EEG) in the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF-HRV (p = 0.005) but not HF-HRV (p=0.71). Anger Recall did not change HRV (p-values > 0.10). The SCWT produced decreases in HF-HRV (p = 0.001) as well as LF-HRV (p = 0.001). The magnitude of feeling "happy" during Happiness Recall was positively correlated with ΔHF-HRV (p = 0.050), whereas an incongruent mood state ("frustrated") was associated with smaller ΔHF-HRV (p = 0.070). Associations between frontal EEG activation and HRV responses were mostly non-significant, except for increased right frontal activation during Happiness Recall which was associated with a decrease in LF/HF ratio (p = 0.009). It is concluded that positive and negative mood induction result in differential HRV responses, which is related to both task valence and the intensity of task-induced emotions. PMID:21182891

  10. Active Control of a Moving Noise SOURCE—EFFECT of Off-Axis Source Position

    NASA Astrophysics Data System (ADS)

    GUO, J.; PAN, J.; HODGSON, M.

    2002-03-01

    An optimally arranged multiple-channel active-control system is known to be able to create a large quiet zone in free space for a stationary primary noise source. When the primary noise source moves, the active control of the noise becomes much more difficult, as the primary noise field changes with time in space. In this case, the controller of the control system must respond fast enough to compensate for the change; much research has been focused on this issue. In this paper, it is shown that a moving source also causes difficulties from an acoustical perspective. A moving source not only changes continuously the strengths and phases of the sound field in the space, but also changes the wavefront of the primary sound field continuously. It is known that the efficiency of active noise control is determined mainly by the wavefront matching between the primary and control fields. To keep the control system effective in the case of a moving source, the wavefront of the control field needs to change, in order to continuously match the primary-wavefront change. This paper shows that there are limitations to the control-wavefront change. An optimally pre-arranged, multiple-channel control system is not able to construct a matching wavefront when the primary source moves outside a certain range. In other words, the control system is still able to create a large quiet zone only when the primary source moves within a range around the central axis of the control system. Both the location and the size of the quiet zone change with the location of the primary source.

  11. A turn-key Concept for active cancellation of Global Positioning System L3 Signal

    NASA Astrophysics Data System (ADS)

    Nigra, Lou; Lewis, B. M.; Edgar, C. E.; Perillat, P.; Quintero, L.; Stanimirovic, S.; Gallagher, J. S., III

    2011-01-01

    We present a concept, developed at the National Astronomy and Ionosphere Center (NAIC) at Arecibo, Puerto Rico, for suppression of Global Positioning System (GPS) signals in the 305 m dish radio receiver path prior to backend processing. The subsystem does not require an auxiliary antenna and is intended for easy integration with radio telescope systems with a goal of being a turnkey addition to virtually any facility. We have focused on detection and cancellation of the GPS L3 signal at 1381.05 MHz which, during periodic test modes and particularly during system-wide tests, interfere with observations of objects in a range of redshifts that includes the Coma supercluster, for example. The signal can dynamically change modulation modes and our scheme has demonstrated, through simulations using actual sampled telescope data, the ability to acquire and track these signals as well as detect the mode changes in order to apply cancellation or blanking, as appropriate. The subsystem can also be adapted to GPS L1 (1575.42 MHz), L2C (1227.6 MHz), and others. A follow-up is underway to develop a prototype to deploy and evaluate at NAIC.

  12. Toward Hybrid Position/Force Control for an Active Handheld Micromanipulator

    PubMed Central

    Wells, Trent S.; MacLachlan, Robert A.; Riviere, Cameron N.

    2014-01-01

    Vitreoretinal microsurgery requires precise hand-eye coordination to manipulate delicate structures within the eye on the order of tens of microns. To achieve these tasks, surgeons use tools of diameter 0.9 mm or less to access the eye’s interior structures. The level of force required during these manipulations is often below the human tactile threshold, requiring the surgeon to rely on subtle visual cues or to apply larger forces above the tactile threshold for feedback. However, both of these methods can lead to tissue damage. Excursions can be made into tissues which are not felt by the surgeon, while larger forces have a higher chance of damaging tissue within the eye. To prevent damage to the retina and other anatomy, we present the implementation of hybrid position/force control operating in the sub-tactile force range for a handheld robotic system. This approach resulted in a 42% reduction in the mean force and 52% reduction in maximum force during peeling tasks. PMID:26405560

  13. Aggressive Peripheral CD70-positive T-cell Lymphoma Associated with Severe Chronic Active EBV Infection

    PubMed Central

    Shaffer, Donald R.; Sheehan, Andrea M.; Yi, Zhongzhen; Rodgers, Cheryl C; Bollard, Catherine M; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Gottschalk, Stephen

    2011-01-01

    Severe chronic active Epstein-Barr virus infection (CAEBV) in T or NK cells is a rare complication of latent EBV infection. CAEBV associated T-cell lymphoproliferative disease (LPD) consists of polyclonal lesions as well as aggressive lymphomas. Here we report such a patient. In addition, we show that this primary CAEBV associated T-cell lymphoma expresses CD70 and is sensitive to killing by CD70-specific T cells, identifying CD70 as a potential immunotherapeutic target for CAEBV-associated T-cell lymphoma. PMID:21994111

  14. How to create more supportive supervision for primary healthcare: lessons from Ngamiland district of Botswana: co-operative inquiry group

    PubMed Central

    Nkomazana, Oathokwa; Mash, Robert; Wojczewski, Silvia; Kutalek, Ruth; Phaladze, Nthabiseng

    2016-01-01

    Background Supportive supervision is a way to foster performance, productivity, motivation, and retention of health workforce. Nevertheless there is a dearth of evidence of the impact and acceptability of supportive supervision in low- and middle-income countries. This article describes a participatory process of transforming the supervisory practice of district health managers to create a supportive environment for primary healthcare workers. Objective The objective of the study was to explore how district health managers can change their practice to create a more supportive environment for primary healthcare providers. Design A facilitated co-operative inquiry group (CIG) was formed with Ngamiland health district managers. CIG belongs to the participatory action research paradigm and is characterised by a cyclic process of observation, reflection, planning, and action. The CIG went through three cycles between March 2013 and March 2014. Results Twelve district health managers participated in the inquiry group. The major insights and learning that emerged from the inquiry process included inadequate supervisory practice, perceptions of healthcare workers’ experiences, change in the managers’ supervision paradigm, recognition of the supervisors’ inadequate supervisory skills, and barriers to supportive supervision. Finally, the group developed a 10-point consensus on what they had learnt regarding supportive supervision. Conclusion Ngamiland health district managers have come to appreciate the value of supportive supervision and changed their management style to be more supportive of their subordinates. They also developed a consensus on supportive supervision that could be adapted for use nationally. Supportive supervision should be prioritised at all levels of the health system, and it should be adequately resourced. PMID:27345024

  15. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    SciTech Connect

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella . E-mail: isabella.screpanti@uniroma1.it

    2005-05-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-J{kappa}-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV.

  16. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons

    PubMed Central

    Liu, Zhenyi; Brown, Andrew; Fisher, Dan; Wu, Yumei; Warren, Joe; Cui, Xiaoxia

    2016-01-01

    The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson’s disease. PMID:26886559

  17. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.

    PubMed

    Liu, Zhenyi; Brown, Andrew; Fisher, Dan; Wu, Yumei; Warren, Joe; Cui, Xiaoxia

    2016-01-01

    The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease. PMID:26886559

  18. The influence of vibration type, frequency, body position and additional load on the neuromuscular activity during whole body vibration.

    PubMed

    Ritzmann, Ramona; Gollhofer, Albert; Kramer, Andreas

    2013-01-01

    This study aimed to assess the influence of different whole body vibration (WBV) determinants on the electromyographic (EMG) activity during WBV in order to identify those training conditions that cause highest neuromuscular responses and therefore provide optimal training conditions. In a randomized cross-over study, the EMG activity of six leg muscles was analyzed in 18 subjects with respect to the following determinants: (1) vibration type (side-alternating vibration (SV) vs. synchronous vibration (SyV), (2) frequency (5-10-15-20-25-30 Hz), (3) knee flexion angle (10°-30°-60°), (4) stance condition (forefoot vs. normal stance) and (5) load variation (no extra load vs. additional load equal to one-third of the body weight). The results are: (1) neuromuscular activity during SV was enhanced compared to SyV (P < 0.05); (2) a progressive increase in frequency caused a progressive increase in EMG activity (P < 0.05); (3) the EMG activity was highest for the knee extensors when the knee joint was 60° flexed (P < 0.05); (4) for the plantar flexors in the forefoot stance condition (P < 0.05); and (5) additional load caused an increase in neuromuscular activation (P < 0.05). In conclusion, large variations of the EMG activation could be observed across conditions. However, with an appropriate adjustment of specific WBV determinants, high EMG activations and therefore high activation intensities could be achieved in the selected muscles. The combination of high vibration frequencies with additional load on an SV platform led to highest EMG activities. Regarding the body position, a knee flexion of 60° and forefoot stance appear to be beneficial for the knee extensors and the plantar flexors, respectively. PMID:22538279

  19. Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens.

    PubMed

    Magarvey, Nathan A; Haltli, Brad; He, Min; Greenstein, Michael; Hucul, John A

    2006-06-01

    The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from Streptomyces hygroscopicus NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically. PMID:16723579

  20. Active Learning in a Neuroethics Course Positively Impacts Moral Judgment Development in Undergraduates

    PubMed Central

    Abu-Odeh, Desiree; Dziobek, Derek; Jimenez, Nathalia Torres; Barbey, Christopher; Dubinsky, Janet M

    2015-01-01

    The growing neuroscientific understanding of the biological basis of behaviors has profound social and ethical implications. To address the need for public awareness of the consequences of these advances, we developed an undergraduate neuroethics course, Neuroscience and Society, at the University of Minnesota. Course evolution, objectives, content, and impact are described here. To engage all students and facilitate undergraduate ethics education, this course employed daily reading, writing, and student discussion, case analysis, and team presentations with goals of fostering development of moral reasoning and judgment and introducing application of bioethical frameworks to topics raised by neuroscience. Pre- and post-course Defining Issues Test (DIT) scores and student end-of-course reflections demonstrated that course objectives for student application of bioethical frameworks to neuroethical issues were met. The active-learning, student-centered pedagogical approaches used to achieve these goals serve as a model for how to effectively teach neuroethics at the undergraduate level. PMID:25838802

  1. Biosynthetic Pathway for Mannopeptimycins, Lipoglycopeptide Antibiotics Active against Drug-Resistant Gram-Positive Pathogens

    PubMed Central

    Magarvey, Nathan A.; Haltli, Brad; He, Min; Greenstein, Michael; Hucul, John A.

    2006-01-01

    The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from Streptomyces hygroscopicus NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically. PMID:16723579

  2. Increased numbers and functional activity of CD56+ T cells in healthy cytomegalovirus positive subjects

    PubMed Central

    Almehmadi, Mazen; Flanagan, Brian F; Khan, Naeem; Alomar, Suliman; Christmas, Stephen E

    2014-01-01

    Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. Proportions of CD56+ T cells were found to be highly significantly increased in cytomegalovirus-seropositive (CMV+) compared with seronegative (CMV−) healthy subjects (9·1 ± 1·5% versus 3·7 ± 1·0%; P < 0·0001). Proportions of CD56+ T cells expressing CD28, CD62L, CD127, CD161 and CCR7 were significantly lower in CMV+ than CMV− subjects but those expressing CD4, CD8, CD45RO, CD57, CD58, CD94 and NKG2C were significantly increased (P < 0·05), some having the phenotype of T effector memory cells. Levels of pro-inflammatory cytokines and CD107a were significantly higher in CD56+ T cells from CMV+ than CMV− subjects following stimulation with CMV antigens. This also resulted in higher levels of proliferation in CD56+ T cells from CMV+ than CMV− subjects. Using Class I HLA pentamers, it was found that CD56+ T cells from CMV+ subjects contained similar proportions of antigen-specific CD8+ T cells to CD56− T cells in donors of several different HLA types. These differences may reflect the expansion and enhanced functional activity of CMV-specific CD56+ memory T cells. In view of the link between CD56 expression and T-cell cytotoxic function, this strongly implicates CD56+ T cells as being an important component of the cytotoxic T-cell response to CMV in healthy carriers. PMID:24433347

  3. Thusin, a Novel Two-Component Lantibiotic with Potent Antimicrobial Activity against Several Gram-Positive Pathogens

    PubMed Central

    Xin, Bingyue; Zheng, Jinshui; Liu, Hualin; Li, Junhua; Ruan, Lifang; Peng, Donghai; Sajid, Muhammad; Sun, Ming

    2016-01-01

    Due to the rapidly increasing prevalence of multidrug-resistant bacterial strains, the need for new antimicrobial drugs to treat infections has become urgent. Bacteriocins, which are antimicrobial peptides of bacterial origin, are considered potential alternatives to conventional antibiotics and have attracted widespread attention in recent years. Among these bacteriocins, lantibiotics, especially two-component lantibiotics, exhibit potent antimicrobial activity against some clinically relevant Gram-positive pathogens and have potential applications in the pharmaceutical industry. In this study, we characterized a novel two-component lantibiotic termed thusin that consists of Thsα, Thsβ, and Thsβ' (mutation of Thsβ, A14G) and that was isolated from a B. thuringiensis strain BGSC 4BT1. Thsα and Thsβ (or Thsβ') exhibit optimal antimicrobial activity at a 1:1 ratio and act sequentially to affect target cells, and they are all highly thermostable (100°C for 30 min) and pH tolerant (pH 2.0 to 9.0). Thusin shows remarkable efficacy against all tested Gram-positive bacteria and greater activities than two known lantibiotics thuricin 4A-4 and ticin A4, and one antibiotic vancomycin against various bacterial pathogens (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus (MRSA), Staphylococcus sciuri, Enterococcus faecalis, and Streptococcus pneumoniae). Moreover, thusin is also able to inhibit the outgrowth of B. cereus spores. The potent antimicrobial activity of thusin against some Gram-positive pathogens indicates that it has potential for the development of new drugs. PMID:27486447

  4. Thusin, a Novel Two-Component Lantibiotic with Potent Antimicrobial Activity against Several Gram-Positive Pathogens.

    PubMed

    Xin, Bingyue; Zheng, Jinshui; Liu, Hualin; Li, Junhua; Ruan, Lifang; Peng, Donghai; Sajid, Muhammad; Sun, Ming

    2016-01-01

    Due to the rapidly increasing prevalence of multidrug-resistant bacterial strains, the need for new antimicrobial drugs to treat infections has become urgent. Bacteriocins, which are antimicrobial peptides of bacterial origin, are considered potential alternatives to conventional antibiotics and have attracted widespread attention in recent years. Among these bacteriocins, lantibiotics, especially two-component lantibiotics, exhibit potent antimicrobial activity against some clinically relevant Gram-positive pathogens and have potential applications in the pharmaceutical industry. In this study, we characterized a novel two-component lantibiotic termed thusin that consists of Thsα, Thsβ, and Thsβ' (mutation of Thsβ, A14G) and that was isolated from a B. thuringiensis strain BGSC 4BT1. Thsα and Thsβ (or Thsβ') exhibit optimal antimicrobial activity at a 1:1 ratio and act sequentially to affect target cells, and they are all highly thermostable (100°C for 30 min) and pH tolerant (pH 2.0 to 9.0). Thusin shows remarkable efficacy against all tested Gram-positive bacteria and greater activities than two known lantibiotics thuricin 4A-4 and ticin A4, and one antibiotic vancomycin against various bacterial pathogens (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus (MRSA), Staphylococcus sciuri, Enterococcus faecalis, and Streptococcus pneumoniae). Moreover, thusin is also able to inhibit the outgrowth of B. cereus spores. The potent antimicrobial activity of thusin against some Gram-positive pathogens indicates that it has potential for the development of new drugs. PMID:27486447

  5. Position surveillance using one active ranging satellite and time-of-arrival of a signal from an independent satellite

    NASA Technical Reports Server (NTRS)

    Anderson, R. E.; Frey, R. L.; Lewis, J. R.

    1981-01-01

    A satellite-aided mobile communication service was tested for position surveillance, with an automatic responder circuit connected between the vehicle receiver and transmitter, and a receiver coded for signals from another satellite. Using the ATS-6 and GOES satellites, a tone-code ranging transponder was connected between the receiver and transmitter, and a 468 MHz receiver was connected to the responder unit for passive reception of the 100 bit per second timing and data signal. Results showed lines of position derived from the active ranging through ATS-6 to be accurate to approximately 0.1 nautical mile, while the NOAA-GOES signals were accurate to about 1.6 miles. The active ranging bandwidth was 2.44 kHz, and the integration time was 0.1 second, while the limitation on accuracy was the 100 Hz bandwidth. This technique of position surveillance was concluded to be feasible and simple to operate, providing needed, good quality communications to the inland waterways industry.

  6. Exposure to blue wavelength light modulates anterior cingulate cortex activation in response to 'uncertain' versus 'certain' anticipation of positive stimuli.

    PubMed

    Alkozei, Anna; Smith, Ryan; Killgore, William D S

    2016-03-11

    Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms. PMID:26806862

  7. Positive Auto-Antibody Activity With Retina and Optic Nerve in Smokers and Non-Smokers: The Controversy Continues.

    PubMed

    Chin, Eric K; Almeida, David R P; Lam, Khoa V; Keltner, John L; Thirkill, Charles E

    2015-01-01

    Auto-antibodies assist with the diagnosis of ocular paraneoplastic syndromes and autoimmune ocular conditions; however, the frequency of positive test results as a possible precursor to future disease is unknown. The frequency of positive antibodies in heavy smokers who may be at risk for autoimmune-related retinopathy and optic neuropathy was evaluated. Serum antibody activity was evaluated through the use of Western blot reactions from pig retina and optic nerve extract. Fifty-one patients were included: 35 patients were smokers (average: 40.9 pack-year history) and 26 patients had no past smoking history. None of the patients had any visual complaints or known eye disease. Of the patients studied, 76.5% (39 patients: 18 smokers, 21 non-smokers) had positive antiretinal antibodies, and 19.6% (10 patients: 3 smokers, 7 non-smokers) had positive antioptic nerve antibodies. Anti-retinal antibodies were seen in a majority of randomly selected patients with and without a past smoking history. Anti-optic nerve bodies were less common, but more prevalent in those who never smoked. The specificity of these antibodies remains greatly uncertain and clinical correlation is warranted. PMID:26599255

  8. Positive parenting during childhood moderates the impact of recent negative events on cortisol activity in parentally bereaved youth

    PubMed Central

    Roubinov, Danielle S.; Gress-Smith, Jenna; Luecken, Linda J.; Sandler, Irwin N.; Wolchik, Sharlene

    2010-01-01

    Rationale Early parental loss has been associated with neuroendocrine dysregulation in youth; however, the form of cortisol dysregulation varies widely. Identifying risk and protective factors that influence physiological regulation has important implications for understanding the development of mental health problems in parentally bereaved youth. Objectives The current study investigated the prospective effects of positive parenting on the relation between recent negative life events and cortisol activity in adolescents/young adults several years after bereavement. Methods Positive parenting was assessed an average of 18.5 months following parental death. Six years later, adolescents/young adults (N=55) reported on exposure to recent negative life events, and salivary cortisol was assessed before and after a conflict discussion task with their caregiver. The interaction between positive parenting and exposure to recent negative events was used to predict total cortisol output and response to the task. Results Multilevel modeling and the probing of the interaction effect demonstrated that total cortisol output increased with greater exposure to recent negative events among those with lower levels of past positive parenting. These relations were significant over and above current internalizing and externalizing symptoms. Conclusions The current results highlight the need to consider the interactive influence of proximal and distal factors on neuroendocrine functioning for youth exposed to early parental loss. PMID:20521029

  9. Position surveillance using one active ranging satellite and time-of-arrival of a signal from an independent satellite

    NASA Technical Reports Server (NTRS)

    Anderson, R. E.; Frey, R. L.; Lewis, J. R.

    1980-01-01

    Position surveillance using one active ranging/communication satellite and the time-of-arrival of signals from an independent satellite was shown to be feasible and practical. A towboat on the Mississippi River was equipped with a tone-code ranging transponder and a receiver tuned to the timing signals of the GOES satellite. A similar transponder was located at the office of the towing company. Tone-code ranging interrogations were transmitted from the General Electric Earth Station Laboratory through ATS-6 to the towboat and to the ground truth transponder office. Their automatic responses included digital transmissions of time-of-arrival measurements derived from the GOES signals. The Earth Station Laboratory determined ranges from the satellites to the towboat and computed position fixes. The ATS-6 lines-of-position were more precise than 0.1 NMi, 1 sigma, and the GOES lines-of-position were more precise than 1.6 NMi, 1 sigma. High quality voice communications were accomplished with the transponders using a nondirectional antenna on the towboat. The simple and effective surveillance technique merits further evaluation using operational maritime satellites.

  10. Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression.

    PubMed Central

    Wek, R C; Ramirez, M; Jackson, B M; Hinnebusch, A G

    1990-01-01

    GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein kinases. Substitution of a highly conserved lysine residue in the kinase domain abolished GCN2 regulatory function in vivo and its ability to autophosphorylate in vitro, indicating that GCN2 acts as a protein kinase in stimulating GCN4 expression. Elevated GCN2 gene dosage led to derepression of GCN4 under nonstarvation conditions; however, we found that GCN2 mRNA and protein levels did not increase in wild-type cells in response to amino acid starvation. Therefore, it appears that GCN2 protein kinase function is stimulated posttranslationally in amino acid-starved cells. Three dominant-constitutive GCN2 point mutations were isolated that led to derepressed GCN4 expression under nonstarvation conditions. Two of the GCN2(Con) mutations mapped in the kinase domain itself. The third mapped just downstream from a carboxyl-terminal segment homologous to histidyl-tRNA synthetase (HisRS), which we suggested might function to detect uncharged tRNA in amino acid-starved cells and activate the adjacent protein kinase moiety. Deletions and substitutions in the HisRS-related sequences and in the carboxyl-terminal segment in which one of the GCN2(Con) mutation mapped abolished GCN2 positive regulatory function in vivo without lowering autophosphorylation activity in vitro. These results suggest that sequences flanking the GCN2 protein kinase moiety are positive-acting domains required to increase recognition of physiological substrates or lower the requirement for uncharged tRNA to activate kinase activity under conditions of amino acid starvation. Images PMID:2188100

  11. Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

    PubMed Central

    2012-01-01

    Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

  12. Positioning activated carbon amendment technologies in a novel framework for sediment management.

    PubMed

    Kupryianchyk, Darya; Rakowska, Magdalena I; Reible, Danny; Harmsen, Joop; Cornelissen, Gerard; van Veggel, Marc; Hale, Sarah E; Grotenhuis, Tim; Koelmans, Albert A

    2015-04-01

    Contaminated sediments can pose serious threats to human health and the environment by acting as a source of toxic chemicals. The amendment of contaminated sediments with strong sorbents like activated C (AC) is a rapidly developing strategy to manage contaminated sediments. To date, a great deal of attention has been paid to the technical and ecological features and implications of sediment remediation with AC, although science in this field still is rapidly evolving. This article aims to provide an update on the recent literature on these features, and provides a comparison of sediment remediation with AC to other sediment management options, emphasizing their full-scale application. First, a qualitative overview of advantages of current alternatives to remediate contaminated sediments is presented. Subsequently, AC treatment technology is critically reviewed, including current understanding of the effectiveness and ecological safety for the use of AC in natural systems. Finally, this information is used to provide a novel framework for supporting decisions concerning sediment remediation and beneficial reuse. PMID:25641867

  13. Structure-activity relationship study at C9 position of kaitocephalin.

    PubMed

    Yasuno, Yoko; Hamada, Makoto; Yoshida, Yuya; Shimamoto, Keiko; Shigeri, Yasushi; Akizawa, Toshifumi; Konishi, Motomi; Ohfune, Yasufumi; Shinada, Tetsuro

    2016-08-01

    Kaitocephalin (KCP) isolated from Eupenicillium shearii PF1191 is an unusual amino acid natural product in which serine, proline, and alanine moieties are liked with carbon-carbon bonds. KCP exhibits potent and selective binding affinity for one of the ionotropic glutamate receptor subtypes, NMDA receptors (Ki=7.8nM). In this study, new structure-activity relationship studies at C9 of KCP were implemented. Eleven new KCP analogs with different substituents at C9 were prepared and employed for binding affinity tests using native ionotropic glutamate receptors. Replacement of the 3,5-dichloro-4-hydroxybenzoyl group of KCP with a 3-phenylpropionyl group resulted in significant loss of binding affinity for NMDARs (Ki=1300nM), indicating an indispensable role of the aromatic ring of KCP in the potent and selective binding to NMDARs. Other analogs showed potent binding affinity in a range of 11-270nM. These findings would directly link to develop useful chemical tools toward imaging and labeling of NMDARs. PMID:27329796

  14. Hysteresis and positive cooperativity as possible regulatory mechanisms of Trypanosoma cruzi hexokinase activity.

    PubMed

    Acosta, Héctor; Cáceres, Ana; González-Marcano, Eglys; Quiñones, Wilfredo; Avilán, Luisana; Dubourdieu, Michel; Concepción, Juan Luis

    2014-12-01

    In Trypanosoma cruzi, the causal agent of Chagas disease, the first six or seven steps of glycolysis are compartmentalized in glycosomes, which are authentic but specialized peroxisomes. Hexokinase (HK), the first enzyme in the glycolytic pathway, has been an important research object, particularly as a potential drug target. Here we present the results of a specific kinetics study of the native HK from T. cruzi epimastigotes; a sigmoidal behavior was apparent when the velocity of the reaction was determined as a function of the concentration of its substrates, glucose and ATP. This behavior was only observed at low enzyme concentration, while at high concentration classical Michaelis-Menten kinetics was displayed. The progress curve of the enzyme's activity displays a lag phase of which the length is dependent on the protein concentration, suggesting that HK is a hysteretic enzyme. The hysteretic behavior may be attributed to slow changes in the conformation of T. cruzi HK as a response to variations of glucose and ATP concentrations in the glycosomal matrix. Variations in HK's substrate concentrations within the glycosomes may be due to variations in the trypanosome's environment. The hysteretic and cooperative behavior of the enzyme may be a form of regulation by which the parasite can more readily adapt to these environmental changes, occurring within each of its hosts, or during the early phase of transition to a new host. PMID:25683029

  15. Autophagy Activated by Bluetongue Virus Infection Plays a Positive Role in Its Replication.

    PubMed

    Lv, Shuang; Xu, Qingyuan; Sun, Encheng; Yang, Tao; Li, Junping; Feng, Yufei; Zhang, Qin; Wang, Haixiu; Zhang, Jikai; Wu, Donglai

    2015-08-01

    Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions. PMID:26287233

  16. Autophagy Activated by Bluetongue Virus Infection Plays a Positive Role in Its Replication

    PubMed Central

    Lv, Shuang; Xu, Qingyuan; Sun, Encheng; Yang, Tao; Li, Junping; Feng, Yufei; Zhang, Qin; Wang, Haixiu; Zhang, Jikai; Wu, Donglai

    2015-01-01

    Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions. PMID:26287233

  17. Exploring pharmacological activities and signaling of morphinans substituted in position 6 as potent agonists interacting with the μ opioid receptor

    PubMed Central

    2014-01-01

    Background Opioid analgesics are the most effective drugs for the treatment of moderate to severe pain. However, they also produce several adverse effects that can complicate pain management. The μ opioid (MOP) receptor, a G protein-coupled receptor, is recognized as the opioid receptor type which primarily mediates the pharmacological actions of clinically used opioid agonists. The morphinan class of analgesics including morphine and oxycodone are of main importance as therapeutically valuable drugs. Though the natural alkaloid morphine contains a C-6-hydroxyl group and the semisynthetic derivative oxycodone has a 6-carbonyl function, chemical approaches have uncovered that functionalizing position 6 gives rise to a range of diverse activities. Hence, position 6 of N-methylmorphinans is one of the most manipulated sites, and is established to play a key role in ligand binding at the MOP receptor, efficacy, signaling, and analgesic potency. We have earlier reported on a chemically innovative modification in oxycodone resulting in novel morphinans with 6-acrylonitrile incorporated substructures. Results This study describes in vitro and in vivo pharmacological activities and signaling of new morphinans substituted in position 6 with acrylonitrile and amido functions as potent agonists and antinociceptive agents interacting with MOP receptors. We show that the presence of a 6-cyano group in N-methylmorphinans has a strong influence on the binding to the opioid receptors and post-receptor signaling. One 6-cyano-N-methylmorphinan of the series was identified as the highest affinity and most selective MOP agonist, and very potent in stimulating G protein coupling and intracellular calcium release through the MOP receptor. In vivo, this MOP agonist showed to be greatly effective against thermal and chemical nociception in mice with marked increased antinociceptive potency than the lead molecule oxycodone. Conclusion Development of such novel chemotypes by targeting

  18. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria.

    PubMed

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Iñigo; Novick, Richard P; Christie, Gail E; Penadés, José R

    2013-08-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  19. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

    PubMed Central

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

    2013-01-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  20. Without peripheral interference, thymic deletion is mediated in a cohort of double-positive cells without classical activation

    PubMed Central

    Zhan, Yifan; Purton, Jared F.; Godfrey, Dale I.; Cole, Timothy J.; Heath, William R.; Lew, Andrew M.

    2003-01-01

    Peripheral activation can cause bystander thymocyte death by eliciting a “cytokine storm.” This event complicates in vivo studies using exogenous ligand-induced models of negative selection. A stable transgenic model that selectively eliminates peripheral CD4 cells has allowed us to analyze negative selection as direct cognate events in two T cell receptor transgenic mice, OT-II and DO11. Whereas cognate peptide induced a massive deletion in double-positive (DP) cells in mice with peripheral CD4 cells, this DP deletion was modest in mice lacking peripheral CD4 cells. Using BrdUrd and annexin V staining, we found that negative selection primarily occurs in a cohort of DP cells and the absence of single-positive (SP) cells is largely caused by reduction in the cohort of DP precursors. Moreover, the fates of DP cells and SP cells after antigen exposure were vastly different. Whereas SP cells up-regulated uniformly their CD69 and CD44 levels, increased their cell size, and survived after antigen exposure, DP cells had less CD69 and CD44 up-regulation, no size change, and promptly died. Thus, negative selection represents an “abortive” activation different from activation-induced cell death of mature T cells. PMID:12538873

  1. Selective anticancer activity of hirsutine against HER2‑positive breast cancer cells by inducing DNA damage.

    PubMed

    Lou, Chenghua; Yokoyama, Satoru; Saiki, Ikuo; Hayakawa, Yoshihiro

    2015-04-01

    Hirsutine is one of the major alkaloids isolated from plants of the Uncaria genus and is known for its cardioprotective, anti‑hypertensive and anti-arrhythmic activities. We recently reported that hirsutine is an anti-metastatic phytochemical by targeting NF-κB activation in a murine breast cancer model. In the present study, we further examined the clinical utility of hirsutine against human breast cancer. Among six distinct human breast cancer cell lines, hirsutine showed strong cytotoxicity against HER2-positive/p53-mutated MDA-MB‑453 and BT474 cell lines. Conversely, HER2-negative/p53 wild‑type MCF-7 and ZR-75-1 cell lines showed resistance against hirsutine-induced cytotoxicity. Hirsutine induced apoptotic cell death in the MDA-MB-453 cells, but not in the MCF-7 cells, through activation of caspases. Furthermore, hirsutine induced the DNA damage response in the MDA-MB-453 cells, but not in the MCF-7 cells, as highlighted by the upregulation of γH2AX expression. Along with the induction of the DNA damage response, the suppression of HER2, NF-κB and Akt pathways and the activation of the p38 MAPK pathway in the MDA-MB-453 cells were observed. Considering that there was no difference between MDA-MB-453 and MCF-7 cells in regards to irinotecan‑induced DNA damage response, our present results indicate the selective anticancer activity of hirsutine in HER2-positive breast cancer by inducing a DNA damage response. PMID:25672479

  2. Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal

    PubMed Central

    Wang, David; Bai, Xiao Xue; Williams, Shaun C.; Hua, Shu Cheng; Kim, Jong-Won; Marshall, Nathaniel S.; D'Rozario, Angela; Grunstein, Ronald R.

    2015-01-01

    Objectives: We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. Design: Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. Setting: University teaching hospital. Participants: Stable CPAP users (n = 23 men with OSA) Measurement and Results: Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P < 0.0001) and fast ratio = (alpha+beta)/(delta+theta) (P < 0.0001) across the 2 days of CPAP withdrawal. The A/D ratio significantly correlated with the driving simulator response time (P = 0.015), steering variation (P = 0.002), and PVT reaction time (P = 0.006). In contrast, individual EEG band power of alpha, beta, theta, and delta did not correlate with any neurocognitive performance. Conclusions: Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal. Citation: Wang D, Bai XX, Williams SC, Hua SC, Kim JW, Marshall NS, D'Rozario A, Grunstein RR. Modafinil increases awake EEG activation and improves performance

  3. Visual Feedback of the Non-Moving Limb Improves Active Joint-Position Sense of the Impaired Limb in Spastic Hemiparetic Cerebral Palsy

    ERIC Educational Resources Information Center

    Smorenburg, Ana R. P.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2011-01-01

    This study examined the active joint-position sense in children with Spastic Hemiparetic Cerebral Palsy (SHCP) and the effect of static visual feedback and static mirror visual feedback, of the non-moving limb, on the joint-position sense. Participants were asked to match the position of one upper limb with that of the contralateral limb. The task…

  4. The bactericidal activities of HMR 3004, HMR 3647 and erythromycin against gram-positive bacilli and development of resistance.

    PubMed

    Fernández-Roblas, R; Calvo, R; Esteban, J; Bryskier, A; Soriano, F

    1999-02-01

    The bactericidal activities of two new ketolides, HMR 3004 and HMR 3647, and the potential to develop resistance to these two antibiotics were studied in Gram-positive bacilli. As judged by time-kill kinetics both ketolides were mostly bacteriostatic, being bactericidal against only highly susceptible isolates of Corynebacterium striatum (two isolates) and Corynebacterium minutissimum (one isolate). Spontaneous resistant mutants were detected in seven of 30 strains tested, mainly in Rhodococcus equi, C. minutissimum and C. striatum, with a very low frequency of mutation (10(-12)-10(-15)). PMID:11252337

  5. A positive association between active lifestyle and hemispheric lateralization for motor control and learning in older adults.

    PubMed

    Wang, Jinsung; D'Amato, Arthur; Bambrough, Jennifer; Swartz, Ann M; Miller, Nora E

    2016-11-01

    Physical activity (PA) is well known to have general health benefits for older adults, but it is unclear whether it can also positively affect brain function involved in motor control and learning. We have previously shown that interlimb transfer of visuomotor adaptation occurs asymmetrically in young adults, while that occurs symmetrically in older adults, which suggests that the lateralized function of each hemisphere during motor tasks is diminished with aging. Here, we investigated the association between the level of PA and hemispheric motor lateralization by comparing the pattern of interlimb transfer following visuomotor adaptation between physically active and inactive older adults. Subjects were divided into two groups based on their PA level (active, inactive). They were further divided into two groups, such that a half of the subjects in each group adapted to a 30° rotation during targeted reaching movements with the left arm first, then with the right arm; and the other half with the right arm first, then with the left arm. Results indicated asymmetrical transfer (from left to right only) in the active subjects, whereas symmetrical transfer (from left to right, and vice versa) was observed in the inactive subjects. These findings suggest that older adults who maintain active lifestyle have a central nervous system that is more intact in terms of its lateralized motor function as compared with those who are inactive. PMID:27481694

  6. Changes in upper-extremity muscle activities due to head position in subjects with a forward head posture and rounded shoulders

    PubMed Central

    Kwon, Jung Won; Son, Sung Min; Lee, Na Kyung

    2015-01-01

    [Purpose] This study investigated upper-extremity muscle activities in natural, ideal, and corrected head positions. [Subjects and Methods] Forty subjects with a forward head posture and rounded shoulder were recruited and randomly assigned to the natural head position group (n = 13), ideal head position group (n = 14), or corrected head position group (n = 13). Muscle activities were measured using a four-channel surface electromyography system at the sternocleidomastoideus, upper and lower trapezius, and serratus anterior muscles on the right side during an overhead reaching task. [Results] The muscle activities of the upper trapezius and serratus anterior differed significantly among head positions. Post hoc tests revealed significant differences between natural and ideal head positions, and natural and ideal head positions for both the upper trapezius and serratus anterior. [Conclusion] Recovery of normal upper trapezius and serratus anterior muscle functions plays an important role in correcting forward head posture and rounded shoulders. PMID:26180310

  7. A Conserved Surface Loop in Type I Dehydroquinate Dehydratases Positions an Active Site Arginine and Functions in Substrate Binding

    SciTech Connect

    Light, Samuel H.; Minasov, George; Shuvalova, Ludmilla; Peterson, Scott N.; Caffrey, Michael; Anderson, Wayne F.; Lavie, Arnon

    2012-04-18

    Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic shikimate pathway. We present three crystal structures of the Salmonella enterica type I DHQD that address the functionality of a surface loop that is observed to close over the active site following substrate binding. Two wild-type structures with differing loop conformations and kinetic and structural studies of a mutant provide evidence of both direct and indirect mechanisms of involvement of the loop in substrate binding. In addition to allowing amino acid side chains to establish a direct interaction with the substrate, closure of the loop necessitates a conformational change of a key active site arginine, which in turn positions the substrate productively. The absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials. The structures and ligand binding insights presented here may inform the design of novel type I DHQD inhibiting molecules.

  8. Arginine Patch Predicts the RNA Annealing Activity of Hfq from Gram-Negative and Gram-Positive Bacteria.

    PubMed

    Zheng, Amy; Panja, Subrata; Woodson, Sarah A

    2016-06-01

    The Sm-protein Hfq facilitates interactions between small non-coding RNA (sRNA) and target mRNAs. In enteric Gram-negative bacteria, Hfq is required for sRNA regulation, and hfq deletion results in stress intolerance and reduced virulence. By contrast, the role of Hfq in Gram-positive is less established and varies among species. The RNA binding and RNA annealing activity of Hfq from Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Bacillus subtilis, and Staphylococcus aureus were compared using minimal RNAs and fluorescence spectroscopy. The results show that RNA annealing activity increases with the number of arginines in a semi-conserved patch on the rim of the Hfq hexamer and correlates with the previously reported requirement for Hfq in sRNA regulation. Thus, the amino acid sequence of the arginine patch can predict the chaperone function of Hfq in sRNA regulation in different organisms. PMID:27049793

  9. A Finger-Pressing Position Detector for Assisting People with Developmental Disabilities to Control Their Environmental Stimulation through Fine Motor Activities with a Standard Keyboard

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang

    2012-01-01

    This study used a standard keyboard with a newly developed finger-pressing position detection program (FPPDP), i.e. a new software program, which turns a standard keyboard into a finger-pressing position detector, to evaluate whether two people with developmental disabilities would be able to actively perform fine motor activities to control their…

  10. Evaluation of the in vitro activity of tigecycline against multiresistant Gram-positive cocci containing tetracycline resistance determinants.

    PubMed

    Borbone, Sonia; Lupo, Agnese; Mezzatesta, Maria Lina; Campanile, Floriana; Santagati, Maria; Stefani, Stefania

    2008-03-01

    This study was undertaken to test the in vitro activity of tigecycline against 117 clinically relevant Gram-positive pathogens and to correlate this activity with their resistance gene content. Overall, tigecycline showed a minimal inhibitory concentration (MIC) range of 0.015-0.5mg/L, able to inhibit potently all multiresistant streptococci, enterococci and MR staphylococci. Tigecycline was active against methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, with MICs for 90% of the organisms (MIC(90)) of 0.25 mg/L and 0.12 mg/L, respectively, being more active than linezolid (MIC(90)=2 mg/L) and quinupristin/dalfopristin (MIC(90)=0.5 and 2-4 mg/L, respectively). Molecular characterisation of resistance determinants demonstrated the concomitant presence of different classes of genes: in particular, tet(M), erm(B) and erm(C) in Streptococcus agalactiae; tet(O), variably associated with different erm genes, in Streptococcus pyogenes; vanA, tet(M) and erm(B) in Enterococcus faecalis, and vanA and erm(B) in Enterococcus faecium. All the MRSA strains harboured SCCmec and erm genes and 50% possessed tet(K) with tet(M) genes. Staphylococcus epidermidis strains were only resistant to erythromycin. These results clearly demonstrate that tigecycline has a MIC(90) range of 0.015-0.5 mg/L both against tetracycline-susceptible and -resistant isolates carrying other resistance determinants, suggesting that this drug could play an important role in the treatment of infections caused by these multiresistant Gram-positive pathogens. PMID:17646087

  11. Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive SKBR3 human breast cancer cells.

    PubMed

    Lee, Jin Sun; Yoon, In Sang; Lee, Myung Sun; Cha, Eun Young; Thuong, Phuong Thien; Diep, Trinh Thi; Kim, Je Ryong

    2013-01-01

    Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. Pristimerin inhibited proliferation in dose- and time-dependent manners in cells. We found it to be effective for suppressing HER2 protein and mRNA expression. Fatty acid synthase (FASN) expression and FASN activity were downregulated by pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 and FASN expression induced by pristimerin altered the levels of Akt and mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets such as phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis for propidium iodide labeling. These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for HER2-positive breast cancers. PMID:23370361

  12. The β2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion.

    PubMed

    Pon, Cindy K; Lane, J Robert; Sloan, Erica K; Halls, Michelle L

    2016-03-01

    Activation of the sympathetic nervous system by stress increases breast cancer metastasis in vivo. Preclinical studies suggest that stress activates β-adrenoceptors (βARs) to enhance metastasis from primary tumors and that β-blockers may be protective in breast cancer. However, the subtype of βAR that mediates this effect, as well as the signaling mechanisms underlying increased tumor cell dissemination, remain unclear. We show that the β2AR is the only functionally relevant βAR subtype in the highly metastatic human breast cancer cell line MDA-MB-231HM. β2AR activation results in elevated cAMP (formoterol pEC50 9.86 ± 0.32), increased intracellular Ca(2+) (formoterol pEC50 8.20 ± 0.33) and reduced phosphorylated ERK (pERK; formoterol pIC50 11.62 ± 0.31). We demonstrate that a highly amplified positive feedforward loop between the cAMP and Ca(2+) pathways is responsible for efficient inhibition of basal pERK. Importantly, activation of the β2AR increased invasion (formoterol area under the curve [AUC] relative to vehicle: 1.82 ± 0.36), which was dependent on the cAMP/Ca(2+) loop (formoterol AUC in the presence of 2'5'-dideoxyadenosine 0.64 ± 0.03, or BAPTA-AM 0.45 ± 0.23) but independent of inhibition of basal pERK1/2 (vehicle AUC with U0126 0.60 ± 0.30). Specifically targeting the positive feedforward cAMP/Ca(2+) loop may be beneficial for the development of therapeutics to slow disease progression in patients with breast cancer. PMID:26578688

  13. Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations

    PubMed Central

    2012-01-01

    Myelodysplastic syndromes (MDS) are often accompanied by autoimmune phenomena. The underlying mechanisms for these associations remain uncertain, although T cell activation seems to be important. Human T-lymphotropic virus (HTLV-1) has been detected in patients with myelodysplastic syndromes, mostly in regions of the world which are endemic for the virus, and where association of HTLV-1 with rheumatological manifestation is not rare. We present here the case of a 58 year old man who presented with cytopenias, leukocytoclastic vasculitis of the skin and glomerulopathy, and was diagnosed as MDS (refractory anemia with excess blasts - RAEB 1). The patient also tested positive for HTLV-1 by PCR. After 8 monthly cycles of 5-azacytidine he achieved a complete hematologic remission. Following treatment, a second PCR for HTLV-1 was carried out and found to be negative. This is the first report in the literature of a HTLV-1-positive MDS with severe autoimmune manifestations, which was treated with the hypomethylating factor 5-azacitidine, achieving cytogenetic remission with concomitant resolution of the autoimmune manifestations, as well as HTLV-1-PCR negativity. HTLV-1-PCR negativity may be due to either immune mediated clearance of the virus, or a potential antiretroviral effect of 5-azacytidine. 5-azacytidine is known for its antiretroviral effects, although there is no proof of its activity against HTLV-1 infection in vivo. PMID:22214262

  14. Postsaccadic activities in the posterior parietal cortex of primates are influenced by both eye movement vectors and eye position.

    PubMed

    Genovesio, Aldo; Brunamonti, Emiliano; Giusti, Maria Assunta; Ferraina, Stefano

    2007-03-21

    Primates explore their visual environment by redirecting the gaze to objects of interest by alternating eye movements and periods of steady fixation. During this task, the fixation point changes frequently in depth. Therefore, the representation of object location based on retinal disparity requires frequent updating. Neural activity was recorded in the lateral intraparietal (LIP) area while monkeys performed saccades between targets in different depths. We report that in the early postsaccadic period, posterior parietal neurons continue to encode the difference in depth between fixation point and targets. About one-third of these neurons are, during the same period, modulated by eye position in depth as well. In the late postsaccadic period, the influence of the previous movement vector dissipates, and parietal neurons are modulated only by the new fixation distance. This result suggests that the postsaccadic activity of area LIP contributes to the dynamic representation of the visual space, and it is compatible with the presence of both a vector subtraction computation and eye-position-dependent gain fields. PMID:17376987

  15. Antimicrobial Activities of Leaf Extracts of Guava (Psidium guajava L.) on Two Gram-Negative and Gram-Positive Bacteria

    PubMed Central

    Biswas, Bipul; Rogers, Kimberly; McLaughlin, Fredrick; Yadav, Anand

    2013-01-01

    Aim. To determine the antimicrobial potential of guava (Psidium guajava) leaf extracts against two gram-negative bacteria (Escherichia coli and Salmonella enteritidis) and two gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) which are some of foodborne and spoilage bacteria. The guava leaves were extracted in four different solvents of increasing polarities (hexane, methanol, ethanol, and water). The efficacy of these extracts was tested against those bacteria through a well-diffusion method employing 50 μL leaf-extract solution per well. According to the findings of the antibacterial assay, the methanol and ethanol extracts of the guava leaves showed inhibitory activity against gram-positive bacteria, whereas the gram-negative bacteria were resistant to all the solvent extracts. The methanol extract had an antibacterial activity with mean zones of inhibition of 8.27 and 12.3 mm, and the ethanol extract had a mean zone of inhibition of 6.11 and 11.0 mm against B. cereus and S. aureus, respectively. On the basis of the present finding, guava leaf-extract might be a good candidate in the search for a natural antimicrobial agent. This study provides scientific understanding to further determine the antimicrobial values and investigate other pharmacological properties. PMID:24223039

  16. The use of nanometer tetrabasic lead sulfate as positive active material additive for valve regulated lead-acid battery

    NASA Astrophysics Data System (ADS)

    Lang, Xiaoshi; Wang, Dianlong; Hu, Chiyu; Tang, Shenzhi; Zhu, Junsheng; Guo, Chenfeng

    2014-12-01

    Conventional tetrabasic lead sulfate used as positive active material additive shows the results of the low effective lead dioxide conversion rate due to the large grain size and crossed the crystal structure. In this paper, we study on a type of nanometer tetrabasic lead sulfate. Through the XRD and SEM test and Material Studio software calculation, the purity of tetrabasic lead sulfate is very high, the grain size of the nanometer 4BS is almost unanimous, and can be controlled below 200 nm. When charged and discharged in 1.75 V-2.42 V with the current density of 40 mA g-1, 80 mA g-1 and 160 mA g-1, the effective lead dioxide conversion rate of nanometer 4BS after formation can achieve to 83.48%, 71.42%, and 66.96%. Subsequently, the nanometer 4BS as additive is added to positive paste of lead-acid battery. When the batteries are tested galvanostatically between 1.75 V and 2.42 V at 0.25 C charge and 0.5 C discharge rates at room temperature. The ratio of adding nanometer 4BS is 0%, 1% and 4% and the initial discharge specific capacities are 60 mAh g-1, 65 mAh g-1 and 68 mAh g-1. After 80 cycles, the initial discharge capacity of positive active material with 1% nanometer 4BS decreased less than 10%, while adding 4% nanometer 4BS, the initial discharge capacity doesn't decrease obviously.

  17. Calpain-Mediated Positional Information Directs Cell Wall Orientation to Sustain Plant Stem Cell Activity, Growth and Development.

    PubMed

    Liang, Zhe; Brown, Roy C; Fletcher, Jennifer C; Opsahl-Sorteberg, Hilde-Gunn

    2015-09-01

    Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental for development and growth, being essential to confer and maintain epidermal cell identity that allows development beyond the globular embryo stage. We show that DEK1 expression is highest in the actively dividing cells of seeds, meristems and vasculature. We further show that eliminating Arabidopsis DEK1 function leads to changes in developmental cues from the first zygotic division onward, altered microtubule patterns and misshapen cells, resulting in early embryo abortion. Expression of the embryonic marker genes WOX2, ATML1, PIN4, WUS and STM, related to axis organization, cell identity and meristem functions, is also altered in dek1 embryos. By monitoring cell layer-specific DEK1 down-regulation, we show that L1- and 35S-induced down-regulation mainly affects stem cell functions, causing severe shoot apical meristem phenotypes. These results are consistent with a requirement for DEK1 to direct layer-specific cellular activities and set downstream developmental cues. Our data suggest that DEK1 may anchor cell wall positions and control cell division and differentiation, thereby balancing the plant's requirement to maintain totipotent stem cell reservoirs while simultaneously directing growth and organ formation. A role for DEK1 in regulating microtubule-orchestrated cell wall orientation during cell division can explain its effects on embryonic development, and suggests a more general function for calpains in microtubule organization in eukaryotic cells. PMID:26220906

  18. Trends and Predictors of Mortality Among HIV Positive Patients in the Era of Highly Active Antiretroviral Therapy in Uganda

    PubMed Central

    Rubaihayo, John; Tumwesigye, Nazarius M.; Konde-Lule, Joseph; Makumbi, Fredrick; Nakku, Edith J.; Wamani, Henry; Etukoit, Michael B.

    2015-01-01

    Knowledge of mortality trends and predictors among HIV-positive patients in the era of highly active antiretroviral therapy (HAART) in resource poor settings is still limited. The aim of this study was to describe trends and predictors of mortality among HIV-positive patients in the era of HAART in Uganda. Data from 2004 to 2013 for adult HIV-positive patients (≥15 years) obtaining care and treatment from the AIDS Support Organization in Uganda were reviewed for mortality. Descriptive statistics were analyzed by frequencies and cross tabulations. Calendar period was used as a proxy measure for HAART exposure and a time plot of the proportion of HIV-positive patients reporting dead per year was used to describe the trends. Logistic regression was used to determine the predictors of mortality at bivariate and multivariate levels, respectively. We included in the analysis 95,857 HIV positive patients; 64% were female with median age of 33 years (interquartile range 27-40). Of these 36,133 (38%) were initiated on ART and a total of 4279 (4.5%) died; 19.5% (835/4279) of those who died had an opportunistic infection. Overall, mortality first increased between 2004 and 2006 and thereafter substantially declined (X2trend=211.9, P<0.001). Mortality was relatively higher in Eastern Uganda compared to other geographical areas. Male gender, older age (>45 years), being from Eastern or Northern Uganda, having none or primary education, being unemployed, advanced immunodeficiency (CD4 count <100 cell/µL or WHO stage III or IV) and underweight (<45 kg weight) at HAART initiation and calendar period 2004-2008 were significant predictors of mortality (P<0.001). Overall, the expanding coverage of HAART is associated with a declining trend in mortality among HIV positive patients in Uganda. However, mortality trends differed significantly by geographical area and men remain potentially at higher risk of death probably because of delayed initiation on ART. There is urgent need for

  19. Antibacterial Activity of Stenotrophomonas maltophilia Endolysin P28 against both Gram-positive and Gram-negative Bacteria

    PubMed Central

    Dong, Hongling; Zhu, Chaoyang; Chen, Jingyi; Ye, Xing; Huang, Yu-Ping

    2015-01-01

    Maltocin P28 is a phage-tail like bacteriocin produced by Stenotrophomonas maltophilia P28. The ORF8 of maltocin P28 gene cluster is predicted to encode an endolysin and we name it endolysin P28. Sequence analysis revealed that it contains the lysozyme_like superfamily conserved domain. Endolysin P28 has the four consensus motifs as that of Escherichia coli phage lambda gpR. In this study, endolysin P28 was expressed in E. coli BL21 (DE3) and purified with a C-terminal oligo-histidine tag. The antibacterial activity of endolysin P28 increased as the temperature rose from 25 to 45°C. Thermostability assays showed that endolysin P28 was stable up to 50°C, while its residual activity was reduced by 55% after treatment at 70°C for 30 min. Acidity and high salinity could enhance its antibacterial activity. Endolysin P28 exhibited a broad antibacterial activity against 14 out of 16 tested Gram-positive and Gram-negative bacteria besides S. maltophilia. Moreover, it could effectively lyse intact Gram-negative bacteria in the absence of ethylenediaminetetraacetic acid as an outer membrane permeabilizer. Therefore, the characteristics of endolysin P28 make it a potential therapeutic agent against multi-drug-resistant pathogens. PMID:26635765

  20. Positional specificity of a phospholipase A activity induced by wounding, systemin, and oligosaccharide elicitors in tomato leaves

    PubMed Central

    Narvaez-Vasquez, J; Florin-Christensen, J; Ryan, CA

    1999-01-01

    Phospholipase A (PLA) activity, as measured by the accumulation of (14)C-lysophosphatidylcholine in leaves of tomato plants, increased rapidly and systemically in response to wounding. The increase in PLA activity in the systemic unwounded leaves was biphasic in wild-type tomato plants, peaking at 15 min and again at 60 min, but the second peak of activity was absent in transgenic prosystemin antisense plants. Supplying young excised tomato plants with the polypeptide hormone systemin also caused (14)C-lysophosphatidylcholine to increase to levels similar to those induced by wounding, but the increase in activity persisted for >2 hr. Antagonists of systemin blocked both the release of (14)C-lysophosphatidylcholine and the accumulation of defense proteins in response to systemin. (14)C-lysophosphatidylcholine levels did not increase in response to jasmonic acid. Chemical acylation of the lysophosphatidylcholine produced by wounding, systemin, and oligosaccharide elicitors followed by enzymatic hydrolysis with lipases of known specificities demostrated that the lysophosphatidylcholine is generated by a PLA with specificity for the sn-2 position. PMID:10559447

  1. Activation of NADPH-diaphorase-positive projections to the rostral ventrolateral medulla following cardiac mechanoreceptor stimulation in the conscious rat.

    PubMed

    Kantzides, A; Badoer, E

    2006-06-01

    Stimulation of cardiac mechanoreceptors during volume expansion elicits reflex compensatory changes in sympathetic nerve activity (SNA). The hypothalamic paraventricular nucleus (PVN) and nucleus of the tractus solitarius (NTS) are autonomic regions known to contribute to this reflex. Both of these nuclei project to the rostral ventrolateral medulla (RVLM), critical in the tonic generation of SNA. Recent reports from our laboratory show that these pathways 1) are activated following cardiac mechanoreceptor stimulation, and 2) produce nitric oxide, known to influence SNA. The aims of the present study were to determine whether 1) the activated neurons within the PVN and NTS were nitrergic and 2) these neurons projected to the RVLM. Animals were prepared, under general anesthesia, by microinjection of a retrogradely transported tracer into the pressor region of the RVLM and the placement of a balloon at the right venoatrial junction. In conscious rats, the balloon was inflated to stimulate the cardiac mechanoreceptors or was left uninflated. Balloon inflation elicited a significant increase in Fos-positive neurons in the parvocellular PVN (sevenfold) and NTS (fivefold). In the PVN, 51% of nitrergic neurons and 61% of RVLM-projecting nitrergic neurons were activated. In the NTS, these proportions were 8 and 18%, respectively. The data suggest that nitrergic neurons within the PVN and, to a lesser extent, in the NTS, some of which project to the RVLM, may contribute to the central pathways influencing SNA elicited by cardiac mechanoreceptor stimulation. PMID:16682470

  2. The physical environment and health-enhancing activity during the school commute: global positioning system, geographical information systems and accelerometry.

    PubMed

    McMinn, David; Oreskovic, Nicolas M; Aitkenhead, Matt J; Johnston, Derek W; Murtagh, Shemane; Rowe, David A

    2014-05-01

    Active school travel is in decline. An understanding of the potential determinants of health-enhancing physical activity during the school commute may help to inform interventions aimed at reversing these trends. The purpose of this study was to identify the physical environmental factors associated with health-enhancing physical activity during the school commute. Data were collected in 2009 on 166 children commuting home from school in Scotland. Data on location and physical activity were measured using global positioning systems (GPS) and accelerometers, and mapped using geographical information systems (GIS). Multi-level logistic regression models accounting for repeated observations within participants were used to test for associations between each land-use category (road/track/path, other man-made, greenspace, other natural) and moderate-to-vigorous physical activity (MVPA). Thirty-nine children provided 2,782 matched data points. Over one third (37.1%) of children's school commute time was spent in MVPA. Children commuted approximately equal amounts of time via natural and man-made land-uses (50.2% and 49.8% respectively). Commuting via road/track/path was associated with increased likelihood of MVPA (Exp(B)=1.23, P <0.05), but this association was not seen for commuting via other manmade land-uses. No association was noted between greenspace use and MVPA, but travelling via other natural land-uses was associated with lower odds of MVPA (Exp(B)=0.32, P <0.05). Children spend equal amounts of time commuting to school via man-made and natural land-uses, yet man-made transportation route infrastructure appears to provide greater opportunities for achieving health-enhancing physical activity levels. PMID:24893034

  3. Antibacterial Activity of Sphingoid Bases and Fatty Acids against Gram-Positive and Gram-Negative Bacteria

    PubMed Central

    Fischer, Carol L.; Drake, David R.; Dawson, Deborah V.; Blanchette, Derek R.; Brogden, Kim A.

    2012-01-01

    There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity—the sphingoid bases d-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid—against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. d-Sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection. PMID:22155833

  4. Antimicrobial and Efflux Pump Inhibitory Activity of Caffeoylquinic Acids from Artemisia absinthium against Gram-Positive Pathogenic Bacteria

    PubMed Central

    Fiamegos, Yiannis C.; Kastritis, Panagiotis L.; Exarchou, Vassiliki; Han, Haley; Bonvin, Alexandre M. J. J.; Vervoort, Jacques; Lewis, Kim; Hamblin, Michael R.; Tegos, George P.

    2011-01-01

    Background Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. Methodology/Principal Findings In this study we report the identification and characterization of 4′,5′-O-dicaffeoylquinic acid (4′,5′-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of Gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3′,5′-ODCQA, 4′,5′-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4′,5′-ODCQA with pump inhibitory activity whereas 3′,5′-ODCQA was ineffective. These intitial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. Conclusions/Significance These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the

  5. Muscular activity during uphill cycling: effect of slope, posture, hand grip position and constrained bicycle lateral sways.

    PubMed

    Duc, S; Bertucci, W; Pernin, J N; Grappe, F

    2008-02-01

    Despite the wide use of surface electromyography (EMG) to study pedalling movement, there is a paucity of data concerning the muscular activity during uphill cycling, notably in standing posture. The aim of this study was to investigate the muscular activity of eight lower limb muscles and four upper limb muscles across various laboratory pedalling exercises which simulated uphill cycling conditions. Ten trained cyclists rode at 80% of their maximal aerobic power on an inclined motorised treadmill (4%, 7% and 10%) with using two pedalling postures (seated and standing). Two additional rides were made in standing at 4% slope to test the effect of the change of the hand grip position (from brake levers to the drops of the handlebar), and the influence of the lateral sways of the bicycle. For this last goal, the bicycle was fixed on a stationary ergometer to prevent the lean of the bicycle side-to-side. EMG was recorded from M. gluteus maximus (GM), M. vastus medialis (VM), M. rectus femoris (RF), M. biceps femoris (BF), M. semimembranosus (SM), M. gastrocnemius medialis (GAS), M. soleus (SOL), M. tibialis anterior (TA), M. biceps brachii (BB), M. triceps brachii (TB), M. rectus abdominis (RA) and M. erector spinae (ES). Unlike the slope, the change of pedalling posture in uphill cycling had a significant effect on the EMG activity, except for the three muscles crossing the ankle's joint (GAS, SOL and TA). Intensity and duration of GM, VM, RF, BF, BB, TA, RA and ES activity were greater in standing while SM activity showed a slight decrease. In standing, global activity of upper limb was higher when the hand grip position was changed from brake level to the drops, but lower when the lateral sways of the bicycle were constrained. These results seem to be related to (1) the increase of the peak pedal force, (2) the change of the hip and knee joint moments, (3) the need to stabilize pelvic in reference with removing the saddle support, and (4) the shift of the mass

  6. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    PubMed Central

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  7. Alectinib's activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case series.

    PubMed

    Metro, Giulio; Lunardi, Gianluigi; Bennati, Chiara; Chiarini, Pietro; Sperduti, Isabella; Ricciuti, Biagio; Marcomigni, Luca; Costa, Cinzia; Crinò, Lucio; Floridi, Piero; Gori, Stefania; Chiari, Rita

    2016-09-01

    In the present study we assessed the activity of the next-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) alectinib, in patients with ALK-postive, advanced non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. NSCLCs with ALK-positive disease, as assessed by fluorescence in situ hybridization, and CNS metastases were treated with alectinib 600 mg BID. Included patients were followed prospectively in order to evaluate the efficacy of the drug, with particular emphasis on activity in the CNS. Eleven consecutive patients were enrolled. The majority of them were pretreated with crizotinib (n = 10, 90.9 %), and cranial radiotherapy (n = 8, 72.7 %). Six of the seven patients with measurable CNS disease experienced a CNS response, including three patients who were naïve for cranial radiation. Median duration of response was 8 months. For the whole population, median CNS-progression-free survival (-PFS), systemic-PFS, overall-PFS, overall survival, and 1-year survival were 8, 11, 8, 13 months, and 31.1 %, respectively. Two patients experiencing a CNS response were assessed for alectinib's concentrations in serum and cerebro-spinal fluid (CSF), and showed a CSF-to-serum ratio ranging from 0.001 to 0.003 ng/mL. Alectinib is highly active against CNS metastases from ALK-positive NSCLCs, irrespective of prior treatment(s) with ALK-TKI(s) and/or cranial radiotherapy. The low CSF-to-serum ratio of alectinib suggests that measuring the concentrations of the drug in the CSF may not be a reliable surrogate of its distribution into the CNS. PMID:27324494

  8. Assessment of Effective Ankle Joint Positioning in Strength Training for Intrinsic Foot Flexor Muscles: A Comparison of Intrinsic Foot Flexor Muscle Activity in a Position Intermediate to Plantar and Dorsiflexion with that in Maximum Plantar Flexion Using Needle Electromyography

    PubMed Central

    Hashimoto, Takayuki; Sakuraba, Keishoku

    2014-01-01

    [Purpose] The effectiveness of intrinsic foot flexor strength training performed in the plantar flexion position was examined using needle electromyography. [Subjects] The subjects of this study were 18 healthy men. [Methods] We used needle electromyography to measure the muscle activities of the flexor hallucis brevis (FHB), and the flexor digitorum brevis (FDB) in maximum plantar and an intermediate position. [Results] Significant increases in muscle activities were observed for both FHB and FDB, and the rates of increase from the intermediate position to the plantar flexion position were 43% for FHB and 46% for FDB. [Conclusion] This study demonstrated that it is possible to evaluate intrinsic foot flexors, in addition to the numerous reports on treatment methods focusing on extrinsic foot flexors. Furthermore, the results suggest that toe flexion exercises performed during plantar flexion of the ankle joint are an effective method for intrinsic foot flexor strength training. PMID:24707106

  9. Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells

    PubMed Central

    Della Corte, Carminia Maria; Ciaramella, Vincenza; Mauro, Concetta Di; Castellone, Maria Domenica; Papaccio, Federica; Fasano, Morena; Sasso, Ferdinando Carlo; Martinelli, Erika; Troiani, Teresa; De Vita, Ferdinando; Orditura, Michele; Bianco, Roberto; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Purpose Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. Experimental design Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. Results The combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters. Conclusions Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9. PMID:26673006

  10. Positional effects of hydroxy groups on catalytic activity of proton-responsive half-sandwich Cp*Iridium(III) complexes

    SciTech Connect

    Suna, Yuki; Fujita, Etsuko; Ertem, Mehmed Z.; Wang, Wan-Hui; Kambayashi, Hide; Manaka, Yuichi; Muckerman, James T.; Himeda, Yuichiro

    2014-11-12

    Proton-responsive half-sandwich Cp*Ir(III) complexes possessing a bipyridine ligand with two hydroxy groups at the 3,3'-, 4,4'-, 5,5'- or 6,6'-positions (3DHBP, 4DHBP, 5DHBP, or 6DHBP) were systematically investigated. UV-vis titration data provided average pK a values of the hydroxy groups on the ligands. Both hydroxy groups were found to deprotonate in the pH 4.6–5.6 range for the 4–6DHBP complexes. One of the hydroxy groups of the 3DHBP complex exhibited the low pKa value of < 0.4 because the deprotonation is facilitated by the strong intramolecular hydrogen bond formed between the generated oxyanion and the remaining hydroxy group, which in turn leads to an elevated pKa value of ~13.6 for the second deprotonation step. The crystal structures of the 4– and 6DHBP complexes obtained from basic aqueous solutions revealed their deprotonated forms. The intramolecular hydrogen bond in the 3DHBP complex was also observed in the crystal structures. The catalytic activities of these complexes in aqueous phase reactions, at appropriate pH, for hydrogenation of carbon dioxide (pH 8.5), dehydrogenation of formic acid (pH 1.8), transfer hydrogenation reactions using formic acid/formate as a hydrogen source (pH 7.2 and 2.6) were investigated to compare the positional effects of the hydroxy groups. The 4– and 6DHBP complexes exhibited remarkably enhanced catalytic activities under basic conditions because of the resonance effect of the strong electrondonating oxyanions, whereas the 5DHBP complex exhibited negligible activity despite the presence of electron-donating groups. The 3DHBP complex exhibited relatively high catalytic activity at low pH owing to the one strong electron-donating oxyanion group stabilized by the intramolecular hydrogen bond. DFT calculations were employed to study the mechanism of CO₂ hydrogenation by the 4DHBP and 6DHBP complexes, and comparison of the activation free energies of the H₂ heterolysis and CO

  11. Positional effects of hydroxy groups on catalytic activity of proton-responsive half-sandwich Cp*Iridium(III) complexes

    DOE PAGESBeta

    Suna, Yuki; Fujita, Etsuko; Ertem, Mehmed Z.; Wang, Wan-Hui; Kambayashi, Hide; Manaka, Yuichi; Muckerman, James T.; Himeda, Yuichiro

    2014-11-12

    Proton-responsive half-sandwich Cp*Ir(III) complexes possessing a bipyridine ligand with two hydroxy groups at the 3,3'-, 4,4'-, 5,5'- or 6,6'-positions (3DHBP, 4DHBP, 5DHBP, or 6DHBP) were systematically investigated. UV-vis titration data provided average pK a values of the hydroxy groups on the ligands. Both hydroxy groups were found to deprotonate in the pH 4.6–5.6 range for the 4–6DHBP complexes. One of the hydroxy groups of the 3DHBP complex exhibited the low pKa value of < 0.4 because the deprotonation is facilitated by the strong intramolecular hydrogen bond formed between the generated oxyanion and the remaining hydroxy group, which in turn leadsmore » to an elevated pKa value of ~13.6 for the second deprotonation step. The crystal structures of the 4– and 6DHBP complexes obtained from basic aqueous solutions revealed their deprotonated forms. The intramolecular hydrogen bond in the 3DHBP complex was also observed in the crystal structures. The catalytic activities of these complexes in aqueous phase reactions, at appropriate pH, for hydrogenation of carbon dioxide (pH 8.5), dehydrogenation of formic acid (pH 1.8), transfer hydrogenation reactions using formic acid/formate as a hydrogen source (pH 7.2 and 2.6) were investigated to compare the positional effects of the hydroxy groups. The 4– and 6DHBP complexes exhibited remarkably enhanced catalytic activities under basic conditions because of the resonance effect of the strong electrondonating oxyanions, whereas the 5DHBP complex exhibited negligible activity despite the presence of electron-donating groups. The 3DHBP complex exhibited relatively high catalytic activity at low pH owing to the one strong electron-donating oxyanion group stabilized by the intramolecular hydrogen bond. DFT calculations were employed to study the mechanism of CO₂ hydrogenation by the 4DHBP and 6DHBP complexes, and comparison of the activation free energies of the H₂ heterolysis and CO₂ insertion steps

  12. The StrongWomen Change Clubs: Engaging Residents to Catalyze Positive Change in Food and Physical Activity Environments

    PubMed Central

    Seguin, Rebecca A.; Folta, Sara C.; Nelson, Miriam E.; Heidkamp-Young, Eleanor; Fenton, Mark; Junot, Bridgid

    2014-01-01

    Introduction. The epidemic of obesity is a multifaceted public health issue. Positive policy and environmental changes are needed to support healthier eating and increased physical activity. Methods. StrongWomen Change Clubs (SWCCs) were developed through an academic-community research partnership between researchers at Cornell University and Tufts University and community partners (cooperative extension educators) in rural towns in seven U.S. states. Extension educators served as the local leader and each recruited 10–15 residents to undertake a project to improve some aspect of the nutrition or physical activity environment. Most residents had limited (or no) experience in civic engagement. At 6 and 12 months after implementation, the research team conducted key informant interviews with SWCC leaders to capture their perceptions of program process, benchmark achievement, and self-efficacy. Results. At 12 months, each SWCC had accomplished one benchmark; the majority had completed three or more benchmarks. They described common processes for achieving benchmarks such as building relationships and leveraging stakeholder partnerships. Barriers to benchmark achievement included busy schedules and resistance to and slow pace of change. Conclusion. Findings suggest that community change initiatives that involve stakeholders, build upon existing activities and organizational resources, and establish feasible timelines and goals can successfully catalyze environmental change. PMID:25525441

  13. Positive correlation between the body weight of anestrous goats and their response to the male effect with sexually active bucks.

    PubMed

    Véliz, Francisco G; Poindron, Pascal; Malpaux, Benoît; Delgadillo, J Alberto

    2006-01-01

    In the present study, we analyzed the results of two years of response to the male effect in seasonally anestrous goats to investigate whether the activation of female reproductive activity by the male effect is related to the body weight of the females. Seventy-nine adult female Mexican mixed breed goats were used. The anestrous females were exposed during 15 days to sexually active males, and were classified into three categories according to their mean body weight +/-SD (42 +/- 9 kg) (Light: < or = 33 kg, n = 19; Medium: 34-50 kg, n = 46; Heavy: > or = 51 kg, n = 14). More than 98% of the goats from the Medium and Heavy groups showed at least one estrus behavior within the first 15 days following the introduction of the bucks, versus only 63% of the females from the Light group (P < 0.01). The interval between the introduction of the males and the onset of estrus behavior was longer in the females of the Light and Medium groups (4.2 +/- 0.8 and 3.3 +/- 0.3 days) than in the females of the Heavy group (2.0 +/- 0.2 days; P < 0.03). Also, body weight was negatively correlated with latency to first estrus (Spearman r = -0.57; P < 0.001). These results are in agreement with the hypothesis that the ability of anestrous goats to respond to the male effect is positively influenced by their body weight. PMID:17169312

  14. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    PubMed Central

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F I; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L J M

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. PMID:24979331

  15. The Positive Transcription Elongation Factor b Is an Essential Cofactor for the Activation of Transcription by Myocyte Enhancer Factor 2

    PubMed Central

    Nojima, Masanori; Huang, Yehong; Tyagi, Mudit; Kao, Hung-Ying; Fujinaga, Koh

    2014-01-01

    The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyte enhancer factor 2 (MEF2) family of transcription factors, key regulatory factors for myocyte development. Knockdown of endogenous cyclin T1 in murine C2C12 cells abolishes MEF2-dependent reporter gene expression as well as transcription of endogenous MEF2 target genes, whereas overexpression of P-TEFb enhances MEF2-dependent transcription. P-TEFb interacts with MEF2 both in vitro and in vivo. Activation of MEF2-dependent transcription induced by serum starvation is mediated by a rapid dissociation of P-TEFb from its inhibitory subunit, HEXIM1, and a subsequent recruitment of P-TEFb to MEF2 binding sites in the promoter region of MEF2 target genes. These results indicate that recruitment of P-TEFb is a critical step for stimulation of MEF2-dependent transcription, therefore providing a fundamentally important regulatory mechanism underlying the transcriptional program in muscle cells. PMID:18662700

  16. Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

    PubMed

    Byun, Kyeongho; Hyodo, Kazuki; Suwabe, Kazuya; Ochi, Genta; Sakairi, Yosuke; Kato, Morimasa; Dan, Ippeita; Soya, Hideaki

    2014-09-01

    Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions. PMID:24799137

  17. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea.

    PubMed

    Henderson, Luke A; Fatouleh, Rania H; Lundblad, Linda C; McKenzie, David K; Macefield, Vaughan G

    2016-01-01

    Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function. PMID:27013952

  18. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea

    PubMed Central

    Henderson, Luke A.; Fatouleh, Rania H.; Lundblad, Linda C.; McKenzie, David K.; Macefield, Vaughan G.

    2016-01-01

    Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function. PMID:27013952

  19. Synthesis and antitumor activity evaluation of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at C4-position.

    PubMed

    Zhang, Ying; Yang, Chao-Rui; Tang, Xue; Cao, Sheng-Li; Ren, Ting-Ting; Gao, Man; Liao, Ji; Xu, Xingzhi

    2016-10-01

    A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a-q and 9a-i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action. PMID:27575478

  20. Purification of equine neutrophil lysozyme and its antibacterial activity against gram-positive and gram-negative bacteria.

    PubMed

    Pellegrini, A; Waiblinger, S; Von Fellenberg, R

    1991-01-01

    Lysozyme from equine neutrophil granulocytes was isolated in a pure form by fast performance liquid chromatography, i.e. ion-exchange chromatography and reversed-phase chromatography. The lysozyme lysed Micrococcus luteus, Bacillus subtilis and Staphylococcus lentus and was also bactericidal against the Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Bordetella bronchiseptica, and Serratia marcescens. Staphylococcus aureus and Staphylococcus epidermidis were not lysed. The lysozyme was only very slightly bactericidal for S. epidermidis and S. aureus. Equine neutrophil lysozyme was found to be bactericidal for Gram-positive as well as for Gram-negative bacteria without further treatment. Equine and chicken egg white lysozymes were found to be immunologically related when examined using specific antisera against each of them. Both lysozymes also had very similar specific enzymatic activities against M. luteus membranes. PMID:1803722

  1. Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions

    NASA Astrophysics Data System (ADS)

    Das, Jayajit

    2013-03-01

    Stochastic fluctuations in biochemical reactions can regulate single cell decision processes. Using exact solutions and semi-analytical methods we calculate distributions of the maximum value (N) of species concentrations (Pmax (N)) and the time (t) taken to reach the maximum value (Pmax (t)) in minimal models of stochastic chemical reactions commonly found in cell signaling systems. We find, the presence of positive feedback interactions make Pmax (N) more spread out with a higher ``peakedness'' in Pmax (t) . Thus positive feedback interactions may help single cells to respond sensitively to a stimulus when cell decision processes require upregulation of activated forms of key proteins to a threshold number within a time window. Moreover, unlike other models of strongly correlated random variables such as Brownian walks or fluctuating interfaces, the extreme value distributions for the chemical reactions display multiscaling behavior emphasizing the presence of many time scales in cell signaling kinetics. This work was funded by the Research Institute at the Nationwide Children's Hospital and a grant (1R56AI090115-01A1) from the NIH.

  2. Effect of plate preparation on active-material utilization and cycleability of positive plates in automotive lead/acid batteries

    NASA Astrophysics Data System (ADS)

    Ozgun, H.; Lam, L. T.; Rand, D. A. J.; Bhargava, S. K.

    The power demands from automotive lead/acid batteries are rising steadily with the increasing number of electronic accessories that are being fitted to modern vehicles. In order to meet new levels of performance, automotive batteries have been redesigned to use low-ohmic microporous separators, as well as thinner plates (to increase the number of plates per cell) that are made with a low paste density. This approach, however, has led to a separate problem, namely, an appreciable reduction in battery service life. To redress this situation, a research programme has been implemented in our laboratories to examine, in detail, the effect of plate preparation on the active-material utilization and cycleability of automotive positive plates with grids made from low-antimony alloy. The cycleability is evaluated in terms of repetitive reserve-capacity. The results suggest that a paste formula with a combination of high density and low acid-to-oxide ratio is the most appropriate technology for the production of the thin positive plates that are required in advanced designs of automotive batteries.

  3. Activating health goals reduces (increases) hedonic evaluation of food brands for people who harbor highly positive (negative) affect toward them.

    PubMed

    Connell, Paul M; Mayor, Lauren F

    2013-06-01

    Associations of pleasure and fun with junk foods have the potential to create considerable challenges for efforts to improve diets. The aim of this research was to determine whether activating health goals had the potential to exploit mixed motivations (i.e., health and pleasure) that people have related to food, and subsequently strip junk foods of the expected pleasure derived from them. In study 1, 98 participants evaluated a soft drink brand after being primed (not primed) for health. In study 2, 93 participants evaluated a presweetened breakfast cereal brand after being primed (not primed) for health. In both studies, participants who harbored highly positive feelings for the food brands devalued their hedonic judgments of them when they were primed for health. However, in an unexpected result, participants in both studies who harbored highly negative feelings for the food brands revalued their hedonic judgments of them (i.e., increased the favorability) when they were primed for health. Thus, increasing health salience is only effective in decreasing expected pleasure derived from junk foods for people who harbor positive affect toward junk food brands, and is likely counterproductive for people who harbor negative affect toward junk food brands. PMID:23428938

  4. Synthesis and in vitro antitumour activity of tiazofurin analogues with nitrogen functionalities at the C-2' position.

    PubMed

    Popsavin, Mirjana; Kojić, Vesna; Torović, Ljilja; Svirčev, Miloš; Spaić, Saša; Jakimov, Dimitar; Aleksić, Lidija; Bogdanović, Gordana; Popsavin, Velimir

    2016-03-23

    Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose. A number of potential bioisosteres of 1 bearing acylamido functions at the C-2' position have also been synthesized from the same sugar precursor. In vitro cytotoxicities of target molecules against a number of human tumour cell lines were recorded and compared with those observed for lead molecule 1. Some of the synthesized compounds showed potent in vitro antitumour activity, such as 2'-azido derivative 2, which is the most potent of all molecules under evaluation (IC50 0.004 μM against MCF-7 cells). Flow cytometry data suggest that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of Western blot analysis indicate that the synthesized tiazofurin analogues induce apoptosis in a caspase-dependent way. PMID:26859071

  5. Holistic health: predicting our data future (from inter-operability among systems to co-operability among people).

    PubMed

    Rossi Mori, Angelo; Mazzeo, Marta; Mercurio, Gregorio; Verbicaro, Rita

    2013-04-01

    Data depend on processes; processes depend on organizational models; organizational models depend on regulations and policies. This position paper envisages the future data scenarios and the related research needs by addressing this whole logical chain. A 'smarter health and wellness future' requires the proactive engagement of citizens and of their caregivers, and the cooperation of health professionals across care facilities, with intense usage of mobile communication and connected devices. This ecosystem of people and organizations is currently extremely fragmented. Technology offers the possibility to mediate among the different actors in order to build a functional care team around the specific needs of each individual, i.e. a 'virtual facility'. However, this requires policies and regulations in every jurisdiction that motivate providers and their organizations to collaborate among themselves and with citizens according to explicit individual plans of care provision, to share their goals and negotiate their respective roles with respect to each citizen. Once a collaborative organizational context is established within integrated care models, policy makers could identify a critical mass of relevant shared processes and isolate a set of 'Attention Points' with predictable actors, concerns, activities, and thus highly precise information needs. For each Attention Point, a template for a Context-Specific Profile of the patient could be produced, e.g. as an HL7-CDA schema that fully specifies the mandatory and optional (clinical) data useful to support the care processes and to manage governance indicators. In relation to these predictable Attention Points data sources can be aligned to achieve reasonable coherence and consistency. Attention to data quality can be improved in a context of systematic re-use of the same data by different actors in different contexts. From a collection of profiles it could be possible to set up the core of a multi-purpose "Policy

  6. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    PubMed Central

    Liu, Yi; Piao, Hongyu; Gao, Ying; Xu, Caihong; Tian, Ye; Wang, Lihong; Liu, Jinwen; Tang, Bo; Zou, Meijuan; Cheng, Gang

    2015-01-01

    7-Ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan (CPT-11), is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OH)SN38 and chitosan-(C20-OH)SN38) to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OH)SN38 (CS-(10s)SN38) and chitosan-(C20-OH) SN38 (CS-(20s)SN38) were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC)0–24 of SN38 after intravenously administering CS-(10s)SN38 and CS-(20s)SN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01). A larger AUC0–24 of CS-(20s)SN38 was observed when compared to CS-(10s)SN38 (P<0.05). Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20s)SN38 exhibited better in vivo antitumor activity than CS-(10s)SN38 at a dose of 2.5 mg/kg (P<0.05). In conclusion, both macromolecular prodrug micelles improved the in vivo conversion rate and antitumor activity of SN38, but the prodrug in which C20-OH was conjugated to macromolecular materials could be a more promising platform for SN38 delivery. PMID:25848251

  7. Positive alcohol expectancies mediate the influence of the behavioral activation system on alcohol use: a prospective path analysis.

    PubMed

    Wardell, Jeffrey D; Read, Jennifer P; Colder, Craig R; Merrill, Jennifer E

    2012-04-01

    Gray's (1975, 1987) behavioral activation (BAS) and behavioral inhibition systems (BIS) are thought to underlie sensitivity to reinforcement and punishment, respectively. Consistent with Gray's theory and the Acquired Preparedness model, BAS may facilitate the learning of positive alcohol expectancies (PAEs) over time, leading to increases in drinking. Yet, no prospective tests of this pathway have been reported. The present study investigated whether BAS prospectively predicted PAEs and whether PAEs mediated the association between BAS and subsequent alcohol use. We hypothesized that BAS would influence drinking specifically via enhancement-related PAEs. We also explored the role of BIS in PAEs and drinking. College students (N=557) completed online BAS, PAE, and alcohol use measures in September of their first (T1), second (T2), and third (T3) years of college. We conducted autoregressive path analyses with three BAS subscales and BIS (T1) as predictors, four PAE types (T2) as mediators, and quantity and frequency of drinking (T3) as outcomes. The BAS Fun-Seeking scale was prospectively associated with PAEs, and there was a significant indirect path from Fun-Seeking to alcohol use mediated specifically through activity enhancement PAEs. BIS was positively associated with some PAE types, but did not have indirect effects on drinking. Findings are consistent with both the theory of the BAS and the Acquired Preparedness model, as individuals high on BAS Fun-Seeking may find the rewarding properties of alcohol more reinforcing, leading to stronger enhancement PAEs and increased drinking over time. The prospective design helps establish the temporal association between BAS and alcohol-related learning, and points to the need for prevention efforts that target these at-risk students. PMID:22209025

  8. Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.

    PubMed

    Shih, Jennifer; Bashir, Babar; Gustafson, Karen S; Andrake, Mark; Dunbrack, Roland L; Goldstein, Lori J; Boumber, Yanis

    2015-08-01

    Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions. PMID:26285240

  9. Positive Alcohol Expectancies Mediate the Influence of the Behavioral Activation System on Alcohol Use: A Prospective Path Analysis

    PubMed Central

    Wardell, Jeffrey D.; Read, Jennifer P.; Colder, Craig R.; Merrill, Jennifer E.

    2012-01-01

    Gray’s (1975, 1987) behavioral activation (BAS) and behavioral inhibition systems (BIS) are thought to underlie sensitivity to reinforcement and punishment, respectively. Consistent with Gray’s theory and the Acquired Preparedness model, BAS may facilitate the learning of positive alcohol expectancies (PAEs) over time, leading to increases in drinking. Yet, no prospective tests of this pathway have been reported. The present study investigated whether BAS prospectively predicted PAEs and whether PAEs mediated the association between BAS and subsequent alcohol use. We hypothesized that BAS would influence drinking specifically via enhancement-related PAEs. We also explored the role of BIS in PAEs and drinking. College students (N=557) completed online BAS, PAE, and alcohol use measures in September of their first (T1), second (T2), and third (T3) years of college. We conducted autoregressive path analyses with three BAS subscales and BIS (T1) as predictors, four PAE types (T2) as mediators, and quantity and frequency of drinking (T3) as outcomes. The BAS Fun-Seeking scale was prospectively associated with PAEs, and there was a significant indirect path from Fun-Seeking to alcohol use mediated specifically through activity enhancement PAEs. BIS was positively associated with some PAE types, but did not have indirect effects on drinking. Findings are consistent with both the theory of the BAS and the Acquired Preparedness model, as individuals high on BAS Fun-Seeking may find the rewarding properties of alcohol more reinforcing, leading to stronger enhancement PAEs and increased drinking over time. The prospective design helps establish the temporal association between BAS and alcohol-related learning, and points to the need for prevention efforts that target these at-risk students. PMID:22209025

  10. Positive regulation of the enzymatic activity of gastric H(+),K(+)-ATPase by sialylation of its β-subunit.

    PubMed

    Fujii, Takuto; Watanabe, Midori; Shimizu, Takahiro; Takeshima, Hiroshi; Kushiro, Keiichiro; Takai, Madoka; Sakai, Hideki

    2016-06-01

    The gastric proton pump (H(+),K(+)-ATPase) consists of a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). βHK glycosylation is essential for the apical trafficking and stability of αHK in gastric parietal cells. Here, we report the properties of sialic acids at the termini of the oligosaccharide chains of βHK. Sialylation of βHK was found in LLC-PK1 cells stably expressing αHK and βHK by staining of the cells with lectin-tagged fluorescent polymeric nanoparticles. This sialylation was also confirmed by biochemical studies using sialic acid-binding lectin beads and an anti-βHK antibody. The sialic acids of βHK are cleaved enzymatically by neuraminidase (sialidase) and nonenzymatically by an acidic solution (pH5). Interestingly, the enzymatic activity of H(+),K(+)-ATPase was significantly decreased by cleavage of the sialic acids of βHK. In contrast, βHK was not sialylated in the gastric tubulovesicles prepared from the stomach of fed hogs. The H(+),K(+)-ATPase activity in these tubulovesicles was not significantly altered by neuraminidase. Importantly, the sialylation of βHK was observed in the gastric samples prepared from the stomach of famotidine (a histamine H2 receptor antagonist)-treated rats, but not histamine (an acid secretagogue)-treated rats. The enzymatic activity of H(+),K(+)-ATPase in the samples of the famotidine-treated rats was significantly higher than in the histamine-treated rats. The effects of famotidine were weakened by neuraminidase. These results indicate that βHK is sialylated at neutral or weakly acidic pH, but not at acidic pH, suggesting that the sialic acids of βHK positively regulate the enzymatic activity of αHK. PMID:26922883

  11. Influence of the length and positioning of the antiestrogenic side chain of endoxifen and 4-hydroxytamoxifen on gene activation and growth of estrogen receptor positive cancer cells.

    PubMed

    Maximov, Philipp Y; Fernandes, Daphne J; McDaniel, Russell E; Myers, Cynthia B; Curpan, Ramona F; Jordan, V Craig

    2014-06-12

    Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER. The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer. PMID:24805199

  12. Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells

    PubMed Central

    2015-01-01

    Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER. The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer. PMID:24805199

  13. Peroxisome proliferator-activated receptorβ/δ activation is essential for modulating p-Foxo1/Foxo1 status in functional insulin-positive cell differentiation

    PubMed Central

    Li, L; Li, T; Zhang, Y; Pan, Z; Wu, B; Huang, X; Zhang, Y; Mei, Y; Ge, L; Shen, G; Ge, R-s; Zhu, D; Lou, Y

    2015-01-01

    Peroxisome proliferator-activated receptors (PPARs) participate in energy homeostasis and play essential roles in diabetes therapy through their effects on non-pancreas tissues. Pathological microenvironment may influence the metabolic requirements for the maintenance of stem cell differentiation. Accordingly, understanding the mechanisms of PPARs on pancreatic β-cell differentiation may be helpful to find the underlying targets of disrupted energy homeostasis under the pancreatic disease condition. PPARs are involved in stem cell differentiation via mitochondrial oxidative phosphorylation, but the subtype member activation and the downstream regulation in functional insulin-positive (INS+) cell differentiation remain unclear. Here, we show a novel role of PPARβ/δ activation in determining INS+ cell differentiation and functional maturation. We found PPARβ/δ expression selectively upregulated in mouse embryonic pancreases or stem cells-derived INS+ cells at the pancreatic mature stage in vivo and in vitro. Strikingly, given the inefficiency of generating INS+ cells in vitro, PPARβ/δ activation displayed increasing mouse and human ES cell-derived INS+ cell numbers and insulin secretion. This phenomenon was closely associated with the forkhead box protein O1 (Foxo1) nuclear shuttling, which was dependent on PPARβ/δ downstream PI3K/Akt signaling transduction. The present study reveals the essential role of PPARβ/δ activation on p-Foxo1/Foxo1 status, and in turn, determining INS+ cell generation and insulin secretion via affecting pancreatic and duodenal homeobox-1 expression. The results demonstrate the underlying mechanism by which PPARβ/δ activation promotes functional INS+ cell differentiation. It also provides potential targets for anti-diabetes drug discovery and hopeful clinical applications in human cell therapy. PMID:25855963

  14. Peroxisome proliferator-activated receptorβ/δ activation is essential for modulating p-Foxo1/Foxo1 status in functional insulin-positive cell differentiation.

    PubMed

    Li, L; Li, T; Zhang, Y; Pan, Z; Wu, B; Huang, X; Zhang, Y; Mei, Y; Ge, L; Shen, G; Ge, R-s; Zhu, D; Lou, Y

    2015-01-01

    Peroxisome proliferator-activated receptors (PPARs) participate in energy homeostasis and play essential roles in diabetes therapy through their effects on non-pancreas tissues. Pathological microenvironment may influence the metabolic requirements for the maintenance of stem cell differentiation. Accordingly, understanding the mechanisms of PPARs on pancreatic β-cell differentiation may be helpful to find the underlying targets of disrupted energy homeostasis under the pancreatic disease condition. PPARs are involved in stem cell differentiation via mitochondrial oxidative phosphorylation, but the subtype member activation and the downstream regulation in functional insulin-positive (INS+) cell differentiation remain unclear. Here, we show a novel role of PPARβ/δ activation in determining INS+ cell differentiation and functional maturation. We found PPARβ/δ expression selectively upregulated in mouse embryonic pancreases or stem cells-derived INS+ cells at the pancreatic mature stage in vivo and in vitro. Strikingly, given the inefficiency of generating INS+ cells in vitro, PPARβ/δ activation displayed increasing mouse and human ES cell-derived INS+ cell numbers and insulin secretion. This phenomenon was closely associated with the forkhead box protein O1 (Foxo1) nuclear shuttling, which was dependent on PPARβ/δ downstream PI3K/Akt signaling transduction. The present study reveals the essential role of PPARβ/δ activation on p-Foxo1/Foxo1 status, and in turn, determining INS+ cell generation and insulin secretion via affecting pancreatic and duodenal homeobox-1 expression. The results demonstrate the underlying mechanism by which PPARβ/δ activation promotes functional INS+ cell differentiation. It also provides potential targets for anti-diabetes drug discovery and hopeful clinical applications in human cell therapy. PMID:25855963

  15. Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia

    PubMed Central

    Chan, Steven M.; Weng, Andrew P.; Tibshirani, Robert; Aster, Jon C.

    2007-01-01

    Constitutive Notch activation is required for the proliferation of a subgroup of T-cell acute lymphoblastic leukemia (T-ALL). Downstream pathways that transmit pro-oncogenic signals are not well characterized. To identify these pathways, protein microarrays were used to profile the phosphorylation state of 108 epitopes on 82 distinct signaling proteins in a panel of 13 T-cell leukemia cell lines treated with a gamma-secretase inhibitor (GSI) to inhibit Notch signals. The microarray screen detected GSI-induced hypophosphorylation of multiple signaling proteins in the mTOR pathway. This effect was rescued by expression of the intracellular domain of Notch and mimicked by dominant negative MAML1, confirming Notch specificity. Withdrawal of Notch signals prevented stimulation of the mTOR pathway by mitogenic factors. These findings collectively suggest that the mTOR pathway is positively regulated by Notch in T-ALL cells. The effect of GSI on the mTOR pathway was independent of changes in phosphatidylinositol-3 kinase and Akt activity, but was rescued by expression of c-Myc, a direct transcriptional target of Notch, implicating c-Myc as an intermediary between Notch and mTOR. T-ALL cell growth was suppressed in a highly synergistic manner by simultaneous treatment with the mTOR inhibitor rapamycin and GSI, which represents a rational drug combination for treating this aggressive human malignancy. PMID:17363738

  16. Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals

    PubMed Central

    Fu, Lin; Wu, Hailong; Cheng, Steven Y; Gao, Daming; Zhang, Lei; Zhao, Yun

    2016-01-01

    Hedgehog signaling plays very important roles in development and cancers. Vertebrates have three transcriptional factors, Gli1, Gli2 and Gli3. Among them, Gli3 is a very special transcriptional factor which closely resembles Cubitus interruptus (Ci, in Drosophila) structurally and functionally as a ‘double agent’ for Shh target gene expression. Here we show that Gli3 full-length, but not the truncated form, can be methylated at K436 and K595. This methylation is specifically catalyzed by Set7, a lysine methyltransferase (KMT). Methylation at K436 and K595 respectively increases the stability and DNA binding ability of Gli3, resulting in an enhancement of Shh signaling activation. Furthermore, functional experiments indicate that the Gli3 methylation contributes to the tumor growth and metastasis in non-small cell lung cancer in vitro and in vivo. Therefore, we propose that Set7 mediated methylation is a novel PTM of Gli3, which positively regulates the transactivity of Gli3 and the activation of Shh signaling. DOI: http://dx.doi.org/10.7554/eLife.15690.001 PMID:27146893

  17. Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes.

    PubMed

    Zhou, Jiyin; Zhou, Shiwen

    2010-12-15

    Berberine has hypoglycemic and hypolipidemic effects on diabetic rats. This study investigated the relationship between hypoglycemic and hypolipidemic effects of berberine and peroxisome proliferator-activated receptors (PPARs) and positive transcription elongation factor b (P-TEFb) (including cyclin-dependent kinase 9 (CDK9) and cyclin T1) in white adipose tissue of diabetic rats and RNA interference-treated 3T3-L1 cells. Berberine promoted differentiation and inhibited lipid accumulation of 3T3-L1 cells, further decreased PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression and decreased tumor necrosis factor α content in supernatants of both control and RNA interference-treated 3T3-L1 cells. After a 16-week induction with 35 mg/kg streptozotocin (i.p.) and high-carbohydrate/high-fat diet, diabetic rats were treated with 75, 150 and 300 mg/kg berberine and 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone for another 16 weeks. Berberine decreased white adipose tissue to body weight ratio and adipocyte size and increased adipocyte number. Berberine upregulated PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression in adipose tissue, decreased tumor necrosis factor α and free fatty acid content and increased lipoprotein lipase activity in serum and adipose tissue. Berberine modulated metabolic related PPARs expression and differentiation related P-TEFb expression in adipocytes, which are associated with its hypoglycemic and hypolipidemic effects. PMID:20868663

  18. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth.

    PubMed

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R; Andl, Thomas; Millar, Sarah E; Zhang, Yuhang

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  19. Canine CD4+CD8+ double positive T cells in peripheral blood have features of activated T cells.

    PubMed

    Bismarck, Doris; Schütze, Nicole; Moore, Peter; Büttner, Mathias; Alber, Gottfried; Buttlar, Heiner v

    2012-10-15

    In dogs a CD4(+)CD8(+) double positive T cell subpopulation exists that has not been phenotypically defined yet. We demonstrate that canine CD4(+)CD8(+) T cells are mature CD1a(-) and TCRαβ(+) T cells. To analyse the activation potential of CD4(+)CD8(+) T cells, PBMC from dogs vaccinated against canine distemper virus (CDV) were re-stimulated with CDV. Upon antigen-specific stimulation, the CD4(+)CD8(+) T cell fraction increases and consists nearly exclusively of proliferated cells. Similarly, other features of activated effector/memory T cells such as up-regulation of CD25 and MHC-II as well as down-regulation of CD62L (L-selectin) were observed in CD4(+)CD8(+) T cells after stimulation. Canine CD4(+)CD8(+) T cells are less abundant, but more heterogeneous than porcine ones, comprising a small proportion expressing the β chain of CD8 in addition to the CD8α chain, like human CD4(+)CD8(+) T cells. In summary, this analysis provides the basis for functional characterisation of the in vivo relevance of CD4(+)CD8(+) T cells in T-cell mediated immunity. PMID:22789871

  20. Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals.

    PubMed

    Fu, Lin; Wu, Hailong; Cheng, Steven Y; Gao, Daming; Zhang, Lei; Zhao, Yun

    2016-01-01

    Hedgehog signaling plays very important roles in development and cancers. Vertebrates have three transcriptional factors, Gli1, Gli2 and Gli3. Among them, Gli3 is a very special transcriptional factor which closely resembles Cubitus interruptus (Ci, in Drosophila) structurally and functionally as a 'double agent' for Shh target gene expression. Here we show that Gli3 full-length, but not the truncated form, can be methylated at K436 and K595. This methylation is specifically catalyzed by Set7, a lysine methyltransferase (KMT). Methylation at K436 and K595 respectively increases the stability and DNA binding ability of Gli3, resulting in an enhancement of Shh signaling activation. Furthermore, functional experiments indicate that the Gli3 methylation contributes to the tumor growth and metastasis in non-small cell lung cancer in vitro and in vivo. Therefore, we propose that Set7 mediated methylation is a novel PTM of Gli3, which positively regulates the transactivity of Gli3 and the activation of Shh signaling. PMID:27146893

  1. Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells.

    PubMed

    Roy, Ananya; Coum, Antoine; Marinescu, Voichita D; Põlajeva, Jelena; Smits, Anja; Nelander, Sven; Uhrbom, Lene; Westermark, Bengt; Forsberg-Nilsson, Karin; Pontén, Fredrik; Tchougounova, Elena

    2015-09-15

    Glioblastoma (GBM) is a high-grade glioma with a complex microenvironment, including various inflammatory cells and mast cells (MCs) as one of them. Previously we had identified glioma grade-dependent MC recruitment. In the present study we investigated the role of plasminogen activator inhibitor 1 (PAI-1) in MC recruitment.PAI-1, a primary regulator in the fibrinolytic cascade is capable of forming a complex with fibrinolytic system proteins together with low-density lipoprotein receptor-related protein 1 (LRP1). We found that neutralizing PAI-1 attenuated infiltration of MCs. To address the potential implication of LRP1 in this process, we used a LRP1 antagonist, receptor-associated protein (RAP), and demonstrated the attenuation of MC migration. Moreover, a positive correlation between the number of MCs and the level of PAI-1 in a large cohort of human glioma samples was observed. Our study demonstrated the expression of LRP1 in human MC line LAD2 and in MCs in human high-grade glioma. The activation of potential PAI-1/LRP1 axis with purified PAI-1 promoted increased phosphorylation of STAT3 and subsequently exocytosis in MCs.These findings indicate the influence of the PAI-1/LRP1 axis on the recruitment of MCs in glioma. The connection between high-grade glioma and MC infiltration could contribute to patient tailored therapy and improve patient stratification in future therapeutic trials. PMID:26164207

  2. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth

    PubMed Central

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R.; Andl, Thomas; Millar, Sarah E.

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  3. Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10

    PubMed Central

    Varga, Jozsef L.; Schally, Andrew V.; Horvath, Judit E.; Kovacs, Magdolna; Halmos, Gabor; Groot, Kate; Toller, Gabor L.; Rekasi, Zoltan; Zarandi, Marta

    2004-01-01

    Antagonists of human growth hormone-releasing hormone (hGHRH) with increased potency and improved enzymatic and chemical stability are needed for potential clinical applications. We synthesized 21 antagonistic analogs of hGHRH(1-29)NH2, substituted at positions 8, 9, and 10 of the common core sequence {phenylacetyl-Tyr1, d-Arg2,28, para-chloro-phenylalanine 6, Arg9/homoarginine 9, Tyr10/O-methyltyrosine 10, α-aminobutyric acid 15, norleucine 27, Har29} hGHRH(1-29)NH2. Inhibitory effects on hGHRH-induced GH release were evaluated in vitro in a superfused rat pituitary system, as well as in vivo after i.v. injection into rats. The binding affinities of the peptides to pituitary GHRH receptors were also determined. Introduction of para-amidinophenylalanine 10 yielded antagonists JV-1-62 and -63 with the highest activities in vitro and lowest receptor dissociation constants (Ki = 0.057-0.062 nM). Antagonists JV-1-62 and -63 also exhibited the strongest effect in vivo, significantly (P < 0.05-0.001) inhibiting hGHRH-induced GH release for at least 1 h. Para-aminophenylalanine 10 and O-ethyltyrosine 10 substitutions yielded antagonists potent in vitro, but His10, 3,3′-diphenylalanine 10, 2-naphthylalanine 10, and cyclohexylalanine 10 modifications were detrimental. Antagonists containing citrulline 9 (in MZ-J-7-72), amidinophenylalanine 9 (in JV-1-65), His9, d-Arg9, citrulline 8, Ala8, d-Ala8, or α-aminobutyric acid 8 substituents also had high activity and receptor affinity in vitro. However, in vitro potencies of analogs with substitution in position 9 correlated poorly with acute endocrine effects in vivo, as exemplified by the weak and/or short inhibitory actions of antagonists JV-1-65 and MZ-J-7-72 on GH release in vivo. Nevertheless, antagonist JV-1-65 was more potent than JV-1-63 in tests on inhibition of the growth of human prostatic and lung cancer lines xenografted into nude mice. This indicates that oncological activity may be based on several mechanisms

  4. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy.

    PubMed

    Srikanth, B Akshaya; Babu, S Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar

    2012-01-01

    To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm(3) with comorbid conditions. PMID:22470896

  5. Production of a bacteriocin by a poultry derived Campylobacter jejuni isolate with antimicrobial activity against Clostridium perfringens and other Gram positive bacteria.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have purified a bacteriocin peptide (termed CUV-3), produced by a poultry cecal isolate of Campylobacter jejuni (strain CUV-3) with inhibitory activity against Gram positive bacteria including Clostridium perfringens (38 strains), Staphylococcus aureus, Staphylococcus epidermidis and Listeria mon...

  6. Is the Modified Tardieu Scale in Semi-Standing Position Better Associated with Knee Extension and Hamstring Activity in Terminal Swing than the Supine Tardieu?

    ERIC Educational Resources Information Center

    Faber, Irene R.; Nienhuis, Bart; Rijs, Nique P. A. M.; Geurts, Alexander C. H.; Duysens, Jacques

    2008-01-01

    The aim of this study was to investigate whether the modified Tardieu scale (MTS) in a semi-standing position, used for the assessment of hamstrings spasticity, was better associated with knee extension and hamstrings activity in terminal swing than the MTS in a supine position in children with cerebral palsy (CP). Seven children diagnosed with…

  7. A perfect storm: examining the synergistic effects of negative and positive emotional instability on promoting weight loss activities in anorexia nervosa.

    PubMed

    Selby, Edward A; Cornelius, Talea; Fehling, Kara B; Kranzler, Amy; Panza, Emily A; Lavender, Jason M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Crow, Scott J; Peterson, Carol B; Le Grange, Daniel

    2015-01-01

    Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as "emotional instability." The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed. PMID:26379588

  8. A perfect storm: examining the synergistic effects of negative and positive emotional instability on promoting weight loss activities in anorexia nervosa

    PubMed Central

    Selby, Edward A.; Cornelius, Talea; Fehling, Kara B.; Kranzler, Amy; Panza, Emily A.; Lavender, Jason M.; Wonderlich, Stephen A.; Crosby, Ross D.; Engel, Scott G.; Mitchell, James E.; Crow, Scott J.; Peterson, Carol B.; Grange, Daniel Le

    2015-01-01

    Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as “emotional instability.” The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed. PMID:26379588

  9. Peroxisome proliferator-activated receptor δ (PPARδ) induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTor activation

    PubMed Central

    Yuan, Hongyan; Lu, Jin; Xiao, Junfeng; Upadhyay, Geeta; Umans, Rachel; Kallakury, Bhaskar; Yin, Yuhzi; Fant, Michael E.; Kopelovich, Levy; Glazer, Robert I.

    2013-01-01

    The peroxisome proliferator-activated receptor-δ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In the present study, we describe a new transgenic mouse model in which activation of PPARδ in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathological changes that culminated in the appearance of estrogen receptor- and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPARδ ligand GW501516 reduced tumor latency to five months. Histopathological changes occurred concurrently with an increase in an inflammatory, invasive, metabolic and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning one week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTor signaling that were attenuated by treatment with the mTor inhibitor everolimus. Our findings are the first to demonstrate a direct role of PPARδ in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. PMID:23811944

  10. Short-term and long-term reproducibility of lung tumor position using active breathing control (ABC)

    SciTech Connect

    Koshani, Rojano . E-mail: rkashani@umich.edu; Balter, James M.; Hayman, James A.; Henning, George T.; Herk, Marcel van

    2006-08-01

    Purpose: To evaluate the short-term and long-term reproducibility of lung tumor position for scans acquired using an active breathing control (ABC) device. Methods and Materials: Ten patients with lung cancer were scanned over three sessions during the course of treatment. For each session, two scans were acquired at deep inhale, and one scan each at half of deep inhale and at exhale. Long-term reproducibility was evaluated by comparing the same breathing state scans from two sessions, with setup variation removed by skeletal alignment. Tumor alignment was based on intensity matching of a small volume around the tumor. For short-term reproducibility, the two inhale volumes from the same session were compared. Results: For the short-term reproducibility, the mean and the standard deviation (SD) of the displacement of the center of tumor were 0.0 (1.5) mm in anteroposterior (AP), 0.3 (1.4) mm in superior/inferior (SI), and 0.2 (0.7) mm in right/left (RL) directions. For long-term reproducibility, the mean (SD) were -1.3 (3.1) mm AP, -0.5 (3.8) mm SI, and 0.3 (1.6) mm RL for inhale and -0.2 (2.8) mm AP, 0.2 (2.1) mm SI, and -0.7 (1.1) mm RL for exhale. Conclusion: The ABC device demonstrates very good short-term and long-term reproducibility. Increased long-term variability in position, primarily in the SI and AP directions, indicates the role of tumor-directed localization in combination with breath-held immobilization.

  11. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor positive breast cancer

    PubMed Central

    Meric-Bernstam, Funda; Gonzalez-Angulo, Ana Maria; Ferrer-Lozano, Jaime; Perez-Fidalgo, Jose A.; Cristofanilli, Massimo; Gómez, Henry; Arteaga, Carlos L.; Giltnane, Jennifer; Balko, Justin M.; Cronin, Maureen T; Jarosz, Mirna; Sun, James; Hawryluk, Matthew; Lipson, Doron; Otto, Geoff; Ross, Jeffrey S; Dvir, Addie; Soussan-Gutman, Lior; Wolf, Ido; Rubinek, Tamar; Gilmore, Lauren; Schnitt, Stuart; Come, Steven E.; Pusztai, Lajos; Stephens, Philip; Brown, Myles; Miller, Vincent A.

    2014-01-01

    Purpose We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone dependent breast cancer and to delineate the functional roles of the most commonly detected alterations. Experimental Design We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER positive (ER+/HER2–) and, as controls, 115 ER negative (ER−) tumors. The ER+ samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes. Results Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER+ metastatic disease. Overall, the frequency of these mutations was 12% (9/76, 95% CI 6%-21%) in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25, 95% CI 7%-41%). These mutations were not detected in primary or treatment naïve ER+ cancer or in any stage of ER− disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments. Conclusions In this study we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER positive breast cancer. PMID:24398047

  12. Expression of different bacterial cytotoxins is controlled by two global transcription factors, CRP and Fis, that co-operate in a shared-recruitment mechanism.

    PubMed

    Rossiter, Amanda E; Godfrey, Rita E; Connolly, Jack A; Busby, Stephen J W; Henderson, Ian R; Browning, Douglas F

    2015-03-01

    Pet is a cytotoxic autotransporter protein secreted by the pathogenic enteroaggregative Escherichia coli strain 042. Expression of Pet is co-dependent on two global transcription regulators: CRP (cyclic AMP receptor protein) and Fis (factor for inversion stimulation). At the pet promoter CRP binds to a single site centred at position -40.5 upstream of the start site for transcription. Due to the suboptimal positioning of this site, CRP alone activates transcription poorly and requires Fis to bind upstream to promote full activation. Here, we show that CRP and Fis control the expression of other important autotransporter toxins, namely Sat from uropathogenic E. coli (UPEC) and SigA from Shigella sonnei, and that this regulation has been conserved in different pathogens. Furthermore, we investigate the mechanism of Fis-mediated co-activation, exploiting a series of semi-synthetic promoters, with similar architecture to the pet promoter. We show that, when bound at position -40.5, CRP recruits RNA polymerase inefficiently and that Fis compensates by aiding polymerase recruitment through a direct protein-protein interaction. We demonstrate that other suitably positioned upstream transcription factors, which directly recruit RNA polymerase, can also compensate for the inappropriate positioning of CRP. We propose that this is a simple 'shared-recruitment' mechanism, by which co-dependence of promoters on two transcription factors could evolve. PMID:25484033

  13. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer

    PubMed Central

    2011-01-01

    Background Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs) are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC) cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312. Results The aldehyde dehydrogenase (ALDH) positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect) and through decrease in telomere length (long-term effect). Administration of this telomerase inhibitor (40 mg/kg) in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls). Combination therapy consisting of irradiation (10Gy) plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo. Conclusions We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer. PMID:21827695

  14. Enhanced antibacterial and anti-biofilm activities of silver nanoparticles against Gram-negative and Gram-positive bacteria

    NASA Astrophysics Data System (ADS)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Kwon, Deug-Nam; Kim, Jin-Hoi

    2014-07-01

    Silver nanoparticles (AgNPs) have been used as antibacterial, antifungal, antiviral, anti-inflammtory, and antiangiogenic due to its unique properties such as physical, chemical, and biological properties. The present study was aimed to investigate antibacterial and anti-biofilm activities of silver nanoparticles alone and in combination with conventional antibiotics against various human pathogenic bacteria. Here, we show that a simple, reliable, cost effective and green method for the synthesis of AgNPs by treating silver ions with leaf extract of Allophylus cobbe. The A. cobbe-mediated synthesis of AgNPs (AgNPs) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the antibacterial and anti-biofilm activity of antibiotics or AgNPs, or combinations of AgNPs with an antibiotic was evaluated using a series of assays: such as in vitro killing assay, disc diffusion assay, biofilm inhibition, and reactive oxygen species generation in Pseudomonas aeruginosa, Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumonia. The results suggest that, in combination with antibiotics, there were significant antimicrobial and anti-biofilm effects at lowest concentration of AgNPs using a novel plant extract of A. cobbe, otherwise sublethal concentrations of the antibiotics. The significant enhancing effects were observed for ampicillin and vancomycin against Gram-negative and Gram-positive bacteria, respectively. These data suggest that combining antibiotics and biogenic AgNPs can be used therapeutically for the treatment of infectious diseases caused by bacteria. This study presented evidence of antibacterial and anti-biofilm effects of A. cobbe-mediated synthesis of AgNPs and their enhanced capacity against various human pathogenic bacteria. These results

  15. Enhanced antibacterial and anti-biofilm activities of silver nanoparticles against Gram-negative and Gram-positive bacteria

    PubMed Central

    2014-01-01

    Silver nanoparticles (AgNPs) have been used as antibacterial, antifungal, antiviral, anti-inflammtory, and antiangiogenic due to its unique properties such as physical, chemical, and biological properties. The present study was aimed to investigate antibacterial and anti-biofilm activities of silver nanoparticles alone and in combination with conventional antibiotics against various human pathogenic bacteria. Here, we show that a simple, reliable, cost effective and green method for the synthesis of AgNPs by treating silver ions with leaf extract of Allophylus cobbe. The A. cobbe-mediated synthesis of AgNPs (AgNPs) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the antibacterial and anti-biofilm activity of antibiotics or AgNPs, or combinations of AgNPs with an antibiotic was evaluated using a series of assays: such as in vitro killing assay, disc diffusion assay, biofilm inhibition, and reactive oxygen species generation in Pseudomonas aeruginosa, Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumonia. The results suggest that, in combination with antibiotics, there were significant antimicrobial and anti-biofilm effects at lowest concentration of AgNPs using a novel plant extract of A. cobbe, otherwise sublethal concentrations of the antibiotics. The significant enhancing effects were observed for ampicillin and vancomycin against Gram-negative and Gram-positive bacteria, respectively. These data suggest that combining antibiotics and biogenic AgNPs can be used therapeutically for the treatment of infectious diseases caused by bacteria. This study presented evidence of antibacterial and anti-biofilm effects of A. cobbe-mediated synthesis of AgNPs and their enhanced capacity against various human pathogenic bacteria. These results

  16. Positive affect as coercive strategy: conditionality, activation and the role of psychology in UK government workfare programmes.

    PubMed

    Friedli, Lynne; Stearn, Robert

    2015-06-01

    Eligibility for social security benefits in many advanced economies is dependent on unemployed and underemployed people carrying out an expanding range of job search, training and work preparation activities, as well as mandatory unpaid labour (workfare). Increasingly, these activities include interventions intended to modify attitudes, beliefs and personality, notably through the imposition of positive affect. Labour on the self in order to achieve characteristics said to increase employability is now widely promoted. This work and the discourse on it are central to the experience of many claimants and contribute to the view that unemployment is evidence of both personal failure and psychological deficit. The use of psychology in the delivery of workfare functions to erase the experience and effects of social and economic inequalities, to construct a psychological ideal that links unemployment to psychological deficit, and so to authorise the extension of state-and state-contracted-surveillance to psychological characteristics. This paper describes the coercive and punitive nature of many psycho-policy interventions and considers the implications of psycho-policy for the disadvantaged and excluded populations who are its primary targets. We draw on personal testimonies of people experiencing workfare, policy analysis and social media records of campaigns opposed to workfare in order to explore the extent of psycho-compulsion in workfare. This is an area that has received little attention in the academic literature but that raises issues of ethics and professional accountability and challenges the field of medical humanities to reflect more critically on its relationship to psychology. PMID:26052120

  17. Positive affect as coercive strategy: conditionality, activation and the role of psychology in UK government workfare programmes

    PubMed Central

    Friedli, Lynne; Stearn, Robert

    2015-01-01

    Eligibility for social security benefits in many advanced economies is dependent on unemployed and underemployed people carrying out an expanding range of job search, training and work preparation activities, as well as mandatory unpaid labour (workfare). Increasingly, these activities include interventions intended to modify attitudes, beliefs and personality, notably through the imposition of positive affect. Labour on the self in order to achieve characteristics said to increase employability is now widely promoted. This work and the discourse on it are central to the experience of many claimants and contribute to the view that unemployment is evidence of both personal failure and psychological deficit. The use of psychology in the delivery of workfare functions to erase the experience and effects of social and economic inequalities, to construct a psychological ideal that links unemployment to psychological deficit, and so to authorise the extension of state—and state-contracted—surveillance to psychological characteristics. This paper describes the coercive and punitive nature of many psycho-policy interventions and considers the implications of psycho-policy for the disadvantaged and excluded populations who are its primary targets. We draw on personal testimonies of people experiencing workfare, policy analysis and social media records of campaigns opposed to workfare in order to explore the extent of psycho-compulsion in workfare. This is an area that has received little attention in the academic literature but that raises issues of ethics and professional accountability and challenges the field of medical humanities to reflect more critically on its relationship to psychology. PMID:26052120

  18. Aberrant activation-induced cytidine deaminase expression in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.

    PubMed

    Shi, Yang; Zhao, Xiaoxian; Durkin, Lisa; Rogers, Heesun Joyce; Hsi, Eric D

    2016-06-01

    Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and plays a critical role in somatic hypermutation and class-switch recombination of immunoglobulin genes. Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carries a poor prognosis and is specifically treated with tyrosine kinase inhibitors. Interestingly, AID has been shown to be aberrantly expressed and functional in Ph+ ALL and is thought to contribute to genetic instability. We hypothesized that AID might be detectable in routinely processed bone marrow biopsies by immunohistochemistry (IHC) and assist in identifying Ph+ ALL. We found that AID was expressed in 26 (70%) of 37 cases of Ph+ ALL but only 1 (2.9%) of 38 cases of Ph- ALL cases. There was a significant difference in AID expression between these 2 ALL groups (P < .001, Fisher exact test). The expression of AID was confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) and correlated with IHC scoring. AID protein is expressed in a large proportion of Ph+ ALL cases at levels detectable by IHC in clinical samples and might be useful to rapidly identify cases likely to have a BCR/ABL1 fusion. PMID:26980048

  19. What can global positioning systems tell us about the contribution of different types of urban greenspace to children’s physical activity?

    PubMed Central

    Lachowycz, Kate; Jones, Andrew P.; Page, Angie S.; Wheeler, Benedict W.; Cooper, Ashley R.

    2013-01-01

    Urban greenspace is hypothesised to be an important location for physical activity in children, but their actual use of the resource to be active is not well known. In this study, global positioning systems (GPS) and accelerometers were used to measure activity within green environments for 902 English children aged 11-12. We summarised activity intensities in different types of greenspace on weekday evenings, weekend days, and by season. Parks were used for as much as 30% of outdoors moderate-vigorous activity at weekends and use was consistent across seasons. The findings suggest the importance of certain types of greenspace to children’s physical activity. PMID:22365385

  20. The Co-operation Schemes Linking Berlin Humboldt University (GDR) with Universities and Academic Establishments in Developing Countries.

    ERIC Educational Resources Information Center

    Klein, Helmut; Zuckert, Ulrich

    1986-01-01

    East Germany's largest university has cooperative agreements and exchanges with six developing countries. The exchange activities include education and training of staff, delegation of university faculty to those countries, collaboration in research, advising, and exchange of experience. (MSE)

  1. Antimicrobial activity of cationic gemini surfactant containing an oxycarbonyl group in the lipophilic portion against gram-positive and gram-negative microorganisms.

    PubMed

    Tatsumi, Taiga; Imai, Yoshitane; Kawaguchi, Kakuhiro; Miyano, Naoko; Ikeda, Isao

    2014-01-01

    We evaluated the antimicrobial activities of a cationic Gemini surfactant, trans-1,4-bis[2-(alkanoyloxy)ethyldimethylammonio]-2-butene dichloride [II-m-2(t-butene)] and its derivatives against Gram-positive and Gram-negative microorganisms. The II-m-2(t-butene) compound was previously shown to have good surface activity and biodegradability. A dodecanoyloxy derivative (m = 12) of II-m-2(t-butene) showed excellent antimicrobial activity against Gram-positive Streptococcus aureus [minimum inhibitory concentration (MIC): 7.8 μg/mL] and Gram-negative Escherichia coli (MIC: 31.2 μg/mL). PMID:24420061

  2. Host Acyl Coenzyme A Binding Protein Regulates Replication Complex Assembly and Activity of a Positive-Strand RNA Virus

    PubMed Central

    Zhang, Jiantao; Diaz, Arturo; Mao, Lan; Ahlquist, Paul

    2012-01-01

    All positive-strand RNA viruses reorganize host intracellular membranes to assemble their replication complexes. Similarly, brome mosaic virus (BMV) induces two alternate forms of membrane-bound RNA replication complexes: vesicular spherules and stacks of appressed double-membrane layers. The mechanisms by which these membrane rearrangements are induced, however, remain unclear. We report here that host ACB1-encoded acyl coenzyme A (acyl-CoA) binding protein (ACBP) is required for the assembly and activity of both BMV RNA replication complexes. ACBP is highly conserved among eukaryotes, specifically binds to long-chain fatty acyl-CoA, and promotes general lipid synthesis. Deleting ACB1 inhibited BMV RNA replication up to 30-fold and resulted in formation of spherules that were ∼50% smaller but ∼4-fold more abundant than those in wild-type (wt) cells, consistent with the idea that BMV 1a invaginates and maintains viral spherules by coating the inner spherule membrane. Furthermore, smaller and more frequent spherules were preferentially formed under conditions that induce layer formation in wt cells. Conversely, cellular karmella structures, which are arrays of endoplasmic reticulum (ER) membranes formed upon overexpression of certain cellular ER membrane proteins, were formed normally, indicating a selective inhibition of 1a-induced membrane rearrangements. Restoring altered lipid composition largely complemented the BMV RNA replication defect, suggesting that ACBP was required for maintaining lipid homeostasis. Smaller and more frequent spherules are also induced by 1a mutants with specific substitutions in a membrane-anchoring amphipathic α-helix, implying that the 1a-lipid interactions play critical roles in viral replication complex assembly. PMID:22345450

  3. Experimental and Computational Mutagenesis To Investigate the Positioning of a General Base within an Enzyme Active Site

    PubMed Central

    2015-01-01

    The positioning of catalytic groups within proteins plays an important role in enzyme catalysis, and here we investigate the positioning of the general base in the enzyme ketosteroid isomerase (KSI). The oxygen atoms of Asp38, the general base in KSI, were previously shown to be involved in anion–aromatic interactions with two neighboring Phe residues. Here we ask whether those interactions are sufficient, within the overall protein architecture, to position Asp38 for catalysis or whether the side chains that pack against Asp38 and/or the residues of the structured loop that is capped by Asp38 are necessary to achieve optimal positioning for catalysis. To test positioning, we mutated each of the aforementioned residues, alone and in combinations, in a background with the native Asp general base and in a D38E mutant background, as Glu at position 38 was previously shown to be mispositioned for general base catalysis. These double-mutant cycles reveal positioning effects as large as 103-fold, indicating that structural features in addition to the overall protein architecture and the Phe residues neighboring the carboxylate oxygen atoms play roles in positioning. X-ray crystallography and molecular dynamics simulations suggest that the functional effects arise from both restricting dynamic fluctuations and disfavoring potential mispositioned states. Whereas it may have been anticipated that multiple interactions would be necessary for optimal general base positioning, the energetic contributions from positioning and the nonadditive nature of these interactions are not revealed by structural inspection and require functional dissection. Recognizing the extent, type, and energetic interconnectivity of interactions that contribute to positioning catalytic groups has implications for enzyme evolution and may help reveal the nature and extent of interactions required to design enzymes that rival those found in biology. PMID:24597914

  4. Calpain-Mediated positional information directs cell wall orientation to sustain plant stem cell activity, growth and development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental f...

  5. Optical and electrical characteristics of in-cloud discharge activity and downward leaders in positive cloud-to-ground lightning flashes

    NASA Astrophysics Data System (ADS)

    Kong, Xiangzhen; Zhao, Yang; Zhang, Tong; Wang, Huaibin

    2015-06-01

    The characteristics of five downward positive cloud-to-ground (CG) flashes were analyzed based on images from a high-speed video camera and electric field (E-field) changes from slow antenna and fast antenna systems. The flashes persisted for 740 ms to 1250 ms. The luminous durations of the leaders ranged from 4 ms to 24 ms. The average 2-D development speeds of the positive leaders ranged from 0.3 × 105 m/s to 2.0 × 105 m/s. The propagation speeds of the positive leaders increased as they approached the ground. Approximately 53.9% of the 89 observed positive CG flashes exhibited isolated monopolar pulses during the leader propagation and immediately prior to the return stroke. The average time interval between adjacent leader pulses was 15 μs according to the E-field changes. Most leaders of positive CG flashes (approximately 67.4%) began in the presence of prolonged and intense in-cloud discharge (IC) activity that ranged from 100 ms to 973 ms. A cloud discharge may be conducive to the formation of positive CG flashes. Generally, a higher occurrence of positive CG flashes corresponded to a higher occurrence of cloud flash, which suggests that positive CG flash can be initiated by a cloud discharge. Four positive CG flashes exhibited one return stroke, and only one flash had two strokes.

  6. Role for intracellular platelet-activating factor in the circulatory failure in a model of gram-positive shock.

    PubMed Central

    De Kimpe, S. J.; Thiemermann, C.; Vane, J. R.

    1995-01-01

    1. This study investigates the effects of two structurally different antagonists of platelet-activating factor (PAF), BN52021 and WEB2086, on the circulatory and renal failure elicited by lipoteichoic acid (LTA) from Staphylococcus aureus (an organism without endotoxin) in anaesthetized rats. 2. Administration of LTA (10 mg kg-1, i.v.) caused hypotension and vascular hyporeactivity to noradrenaline (1 microgram kg-1, i.v.) WEB2086 (5 mg kg-1, i.v., 20 min before and 150 min after LTA) inhibited the delayed fall in mean arterial blood pressure (at 300 min: 99 +/- 6 mmHg vs. 75 +/- 6 mmHg, P < 0.01) and prevented the decrease in pressor response to noradrenaline (at 300 min: 36 +/- 5 mmHg min vs. 17 +/- 5 mmHg min, P < 0.01). Surprisingly, BN52021 (20 mg kg-1, i.v., 20 min before and 150 min after LTA) neither prevented the hypotension (74 +/- 6 mmHg) nor the vascular hyporeactivity (21 +/- 5 mmHg min). However, BN52021 inhibited the hypotension to injections of PAF as well as the circulatory failure elicited by lipopolysaccharides (10 mg kg-1, i.v.). 3. LTA caused an increase in plasma concentration of creatinine from 39 +/- 5 microM (sham-operated) to 70 +/- 8 microM and urea from 4.7 +/- 0.1 to 13.1 +/- 1.6 mM. The renal failure elicited by LTA was significantly inhibited by WEB2086 (creatinine: 45 +/- 4 microM and urea: 5.7 +/- 0.7 mM), but not by BN52021. 4. The induction of nitric oxide synthase activity in lungs by LTA was attenuated by WEB2086 from 98 +/- 17 to 40 +/- 15 pmol L-citrulline 30 min-1 mg-1 protein (P < 0.01), but not by BN52021 (148 +/- 21 pmol L-citrulline 30 min-1 mg-1 protein). Similarly, WEB2086, but not BN52021, inhibited the increase in plasma nitrite concentration associated with the delayed circulatory failure caused by LTA. The release of tumour necrosis factor-alpha (TNF-alpha) after injection of LTA was not attenuated by WEB2086. 5. The induction of nitrite release by cultured macrophages activated with LTA (10 micrograms ml-1 for 24 h

  7. Role for intracellular platelet-activating factor in the circulatory failure in a model of gram-positive shock.

    PubMed

    De Kimpe, S J; Thiemermann, C; Vane, J R

    1995-12-01

    1. This study investigates the effects of two structurally different antagonists of platelet-activating factor (PAF), BN52021 and WEB2086, on the circulatory and renal failure elicited by lipoteichoic acid (LTA) from Staphylococcus aureus (an organism without endotoxin) in anaesthetized rats. 2. Administration of LTA (10 mg kg-1, i.v.) caused hypotension and vascular hyporeactivity to noradrenaline (1 microgram kg-1, i.v.) WEB2086 (5 mg kg-1, i.v., 20 min before and 150 min after LTA) inhibited the delayed fall in mean arterial blood pressure (at 300 min: 99 +/- 6 mmHg vs. 75 +/- 6 mmHg, P < 0.01) and prevented the decrease in pressor response to noradrenaline (at 300 min: 36 +/- 5 mmHg min vs. 17 +/- 5 mmHg min, P < 0.01). Surprisingly, BN52021 (20 mg kg-1, i.v., 20 min before and 150 min after LTA) neither prevented the hypotension (74 +/- 6 mmHg) nor the vascular hyporeactivity (21 +/- 5 mmHg min). However, BN52021 inhibited the hypotension to injections of PAF as well as the circulatory failure elicited by lipopolysaccharides (10 mg kg-1, i.v.). 3. LTA caused an increase in plasma concentration of creatinine from 39 +/- 5 microM (sham-operated) to 70 +/- 8 microM and urea from 4.7 +/- 0.1 to 13.1 +/- 1.6 mM. The renal failure elicited by LTA was significantly inhibited by WEB2086 (creatinine: 45 +/- 4 microM and urea: 5.7 +/- 0.7 mM), but not by BN52021. 4. The induction of nitric oxide synthase activity in lungs by LTA was attenuated by WEB2086 from 98 +/- 17 to 40 +/- 15 pmol L-citrulline 30 min-1 mg-1 protein (P < 0.01), but not by BN52021 (148 +/- 21 pmol L-citrulline 30 min-1 mg-1 protein). Similarly, WEB2086, but not BN52021, inhibited the increase in plasma nitrite concentration associated with the delayed circulatory failure caused by LTA. The release of tumour necrosis factor-alpha (TNF-alpha) after injection of LTA was not attenuated by WEB2086. 5. The induction of nitrite release by cultured macrophages activated with LTA (10 micrograms ml-1 for 24 h

  8. Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure-Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

    PubMed Central

    Sidique, Shyama; Dhanya, Raveendra-Panickar; Sheffler, Douglas J.; Nickols, Hilary Highfield; Yang, Li; Dahl, Russell; Mangravita-Novo, Arianna; Smith, Layton H.; D’Souza, Manoranjan S.; Semenova, Svetlana; Conn, P. Jeffrey; Markou, Athina; Cosford, Nicholas D. P.

    2012-01-01

    Compounds that modulate metabotropic glutamate subtype 2 (mGlu2) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu2 receptor positive allosteric modulators (PAMs). The effects of N-substitution (R1) and substitutions on the aryl ring (R2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu2 receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans. PMID:23009245

  9. Variation in performance at different positions of an ultrasonic VialTweeter--A study based on various physical and chemical activities.

    PubMed

    Tiong, T Joyce; Low, Liang Ee; Teoh, Hui Jiun; Chin, Jit-Kai; Manickam, Sivakumar

    2015-11-01

    Ultrasonic VialTweeter is used for the sonication of small volume samples. It contains a titanium block with 8 holes for vial insertion, to be used simultaneously for batch operation. In this investigation, the ultrasonic and sonochemical performance of ultrasonic VialTweeter has been evaluated at its different positions. Experimental results using calorimetry, ultrasonic capillary effect, sonochemiluminescence and degradation of Rhodamine B showed that the sonochemical activity differs greatly at different positions along the VialTweeter, with positions 3 and 4 showing the maximum efficiency whereas the positions 1 and 2 being the least effective positions. These results were further verified by acoustic pressure simulation, confirming that certain locations in the VialTweeter may not perform in the same way as others due to the variation in acoustic pressure at different locations. PMID:26186833

  10. Monomeric C-reactive protein and Notch-3 co-operatively increase angiogenesis through PI3K signalling pathway.

    PubMed

    Boras, Emhamed; Slevin, Mark; Alexander, M Yvonne; Aljohi, Ali; Gilmore, William; Ashworth, Jason; Krupinski, Jerzy; Potempa, Lawrence A; Al Abdulkareem, Ibrahim; Elobeid, Adila; Matou-Nasri, Sabine

    2014-10-01

    C-reactive protein (CRP) is the most acute-phase reactant serum protein of inflammation and a strong predictor of cardiovascular disease. Its expression is associated with atherosclerotic plaque instability and the formation of immature micro-vessels. We have previously shown that CRP upregulates endothelial-derived Notch-3, a key receptor involved in vascular development, remodelling and maturation. In this study, we investigated the links between the bioactive monomeric CRP (mCRP) and Notch-3 signalling in angiogenesis. We used in vitro (cell counting, wound-healing and tubulogenesis assays) and in vivo (chorioallantoic membrane) angiogenic assays and Western blotting to study the angiogenic signalling pathways induced by mCRP and Notch-3 activator chimera protein (Notch-3/Fc). Our results showed an additive effect on angiogenesis of mCRP stimulatory effect combined with Notch-3/Fc promoting bovine aortic endothelial cell (BAEC) proliferation, migration, tube formation in Matrigel(TM) with up-regulation of phospho-Akt expression. The pharmacological blockade of PI3K/Akt survival pathway by LY294002 fully inhibited in vitro and in vivo angiogenesis induced by mCRP/Notch-3/Fc combination while blocking Notch signalling by gamma-secretase inhibitor (DAPT) partially inhibited mCRP/Notch-3/Fc-induced angiogenesis. Using a BAEC vascular smooth muscle cell co-culture sprouting angiogenesis assay and transmission electron microscopy, we showed that activation of both mCRP and Notch-3 signalling induced the formation of thicker sprouts which were shown later by Western blotting to be associated with an up-regulation of N-cadherin expression and a down-regulation of VE-cadherin expression. Thus, mCRP combined with Notch-3 activator promote angiogenesis through the PI3K/Akt pathway and their therapeutic combination has potential to promote and stabilize vessel formation whilst reducing the risk of haemorrhage from unstable plaques. PMID:24972386

  11. Unique gene alterations are induced in FACS-purified Fos-positive neurons activated during cue-induced relapse to heroin seeking

    PubMed Central

    Fanous, Sanya; Guez-Barber, Danielle H; Goldart, Evan M; Schrama, Regina; Theberge, Florence RM; Shaham, Yavin; Hope, Bruce T

    2012-01-01

    Cue-induced heroin seeking after prolonged withdrawal is associated with neuronal activation and altered gene expression in prefrontal cortex (PFC). However, these previous studies assessed gene expression in all neurons regardless of their activity state during heroin seeking. Using Fos as a marker of neural activity, we describe distinct molecular alterations induced in activated versus non-activated neurons during cue-induced heroin seeking after prolonged withdrawal. We trained rats to self-administer heroin for 10 days (6-h/day) and assessed cue-induced heroin seeking in extinction tests after 14 or 30 days. We used fluorescent-activated cell-sorting (FACS) to purify Fos-positive and Fos-negative neurons from PFC 90 min after extinction testing. Flow cytometry showed that Fos-immunoreactivity was increased in less than 10% of sparsely distributed PFC neurons. mRNA levels of the immediate early genes fosB, arc, egr1, and egr2, as well as npy and map2k6, were increased in Fos-positive, but not Fos-negative, neurons. In support of these findings, double-label immunohistochemistry indicated substantial co-expression of NPY- and Arc-immunoreactivity in Fos-positive neurons. Our data indicate that cue-induced relapse to heroin seeking after prolonged withdrawal induces unique molecular alterations within activated PFC neurons that are distinct from those observed in the surrounding majority of non-activated neurons. PMID:23113797

  12. Tumor suppressor gene co-operativity in compound Patched1 and Suppressor of fused heterozygous mutant mice

    PubMed Central

    Svärd, Jessica; Rozell, Björn; Toftgård, Rune; Teglund, Stephan

    2008-01-01

    Dysregulation of the Hedgehog signaling pathway is central to the development of certain tumor types, including medulloblastoma and basal cell carcinoma (BCC). Patched1 (Ptch1) and Suppressor of fused (Sufu) are two essential negative regulators of the pathway with tumor suppressor activity. Ptch1+/− mice are predisposed to developing medulloblastoma and rhabdomyosarcoma, while Sufu+/− mice develop a skin phenotype characterized by basaloid epidermal proliferations. Here, we have studied tumor development in Sufu+/−Ptch1+/− mice to determine the effect of compound heterozygosity on the onset, incidence, and spectrum of tumors. We found significantly more (2.3-fold) basaloid proliferations in Sufu+/−Ptch1+/− compared to Sufu+/− female, but not male, mice. For medulloblastoma, the cumulative one-year incidence was 1.5-fold higher in Sufu+/−Ptch1+/− compared to Ptch1+/− female mice but this strong trend was not statistically significant. Together this suggests a weak genetic interaction of the two tumor suppressor genes. We noted a few rhabdomyosarcomas and pancreatic cysts in the Sufu+/−Ptch1+/− mice, but the numbers were not significantly different from the single heterozygous mice. Hydrocephalus developed in ∼20% of the Ptch1+/− and Sufu+/−Ptch1+/− but not in Sufu+/− mice. Interestingly, most of the medulloblastomas from the Sufu+/−Ptch1+/− mice had lost expression of the remaining Ptch1 wild-type allele but not the Sufu wild-type allele. On the contrary, Sufu as well as Gli1 and Gli2 expression was upregulated in the medulloblastomas compared to adult cerebellum in Ptch1+/− and Sufu+/−Ptch1+/− mice. This suggests that Sufu expression may be regulated by Hedgehog pathway activity and could constitute another negative feedback loop in the pathway. PMID:18781608

  13. The Council of Europe Co-operation Group to Combat Drug Abuse and Illicit Trafficking in Drugs (the Pompidou Group).

    PubMed

    Nagler, N A

    1987-01-01

    The Pompidou Group was set up in 1971 to provide a forum for exchanging views and concerting action in Western Europe in response to the growing drugs problem. Until 1979 it had no formal status, but in 1980 the Group became part of the Council of Europe with member States being free to choose whether to join or not. Its initial membership of six countries has expanded to 16 members. Every two to three years, ministers from member countries meet to review the work of the Group and to set a new programme of activities. Government officials (Permanent Correspondents) then meet to further the programme by arranging meetings, working groups, seminars, symposia and related activities of experts in particular fields. The Group has considered a wide variety of topics of general interest, which included: European cooperation in the control of drug traffic; problems connected with drug addicts in prison; the care of hard-core addicts; problems related to the staffing of treatment and rehabilitation services; the development of administrative monitoring systems for the assessment of public health and social problems related to drug misuse; drug trafficking on the high seas; the role of the criminal justice system in responding to the needs of drug misusers; methods of reaching young people particularly at risk; problems concerning women and drugs; control services at major European airports; cannabis misuse in Europe; acquired immunodeficiency syndrome among drug misusers; and consideration of elements for inclusion in a new United Nations convention against illicit traffic in narcotic drugs and psychotropic substances. PMID:3620762

  14. Study of GPS Position error during low solar activity period near the Crest of the Equatorial Ionization Anomaly

    NASA Astrophysics Data System (ADS)

    Trivedi, Richa; Gwal, Ashok Kumar; Jain, Sudhir

    In order to study GPS position error, the GPS Ionospheric Scintillation and TEC Monitor (GISTM) based GPS receiver was installed at an equatorial station, Bhopal (23.2° N, 77.4° E, Geomagnetic latitude 14.23˚ N), India. We analyzed the horizontal error and the level of confidence in terms of DRMS & CEP and positional error from fixed GPS point for year 2005-2006. In this paper we observed position error in both storm/disturb as well as quiet ionospheric condition. As the range of error is directly proportional to TEC along the ray path since 6.15 TEC units correspond to the range error of 1 m on L1 frequency, we observed that the change of VTEC is 60 TECU which correspond to 9.76 m for ionospheric disturb day May 15, 2005 (severe geomagnetic storm; SSC at 0239 UT). During the study no scintillation and loss of lock has been observed in both disturb and quiet day except on May 27, 2006 (quiet day). On May 27, 2006 the loss of lock in one satellite has been observed. In order to study the effect of storm/quiet ionospheric condition on GPS position errors, the latitudinal error and longitudinal error in meter is studied. The range of position error was about 2.5 meters during the quiet ionospheric conditions except on June 26, 2006(quite day). The situation became adverse during disturbed ionospheric conditions, with the error reaching up to 5-6 meters. During disturb and quiet ionospheric condition it was observed that the in most of the cases the error point’s lies out side the 95% error ellipse and elongation in the N-E direction. The results have been compared with the earlier ones and discussed in terms of possible source mechanism responsible for the position error at anomaly crest region. Keywords: Total Electron Contents (TEC); Equatorial Ionization Anomaly (EIA); Global Positioning System (GPS).

  15. [Epidemiologic factors in cervical cancer--investigation on 306 pairs of partners. Jiangxi Co-operative Group of Cervical Cancer].

    PubMed

    1986-11-01

    To investigate the epidemiologic factors in Jingan and Tonggu counties, high incidence areas of cervical cancer, the 306 patient-control pairs were studied in 1980. These patients with various stages of cervical cancer were pathologically diagnosed in mass screening. The controls were healthy women of the same tribe and occupation, living in the same village as the patients. The age difference between the patients and the controls were not over 2-3 years. The ratio of the patients to the controls was 1:1. 36 doubtful factors were investigated by direct inquiry with uniform tables. After statistical analysis, it was found that sexual activity, smegma and cervical erosion are the high risk factors in causing cervical cancer. These three factors coexist, the relative risk was 11.2. It suggests that these factors have a comprehensive effect in causing cervical cancer. In view of the above, we suggested a preliminary plan for preventing and blocking of the development of cervical cancer and experiments in Jingan county are being carried out. PMID:3582114

  16. Organized Activity Participation, Positive Youth Development, and the Over-Scheduling Hypothesis. Social Policy Report. Volume 20, Number 4

    ERIC Educational Resources Information Center

    Mahoney, Joseph L.; Harris, Angel L.; Eccles, Jacquelynne S.

    2006-01-01

    There is increasing awareness that how young people spend their time outside of school has consequences for their development. As part of this awareness, interest in organized activities--extracurricular activities, after-school programs, and youth organizations--has grown markedly. On balance, the bulk of research on organized activities has…

  17. Positive Control Mutations in the MyoD Basic Region Fail to Show Cooperative DNA Binding and Transcriptional Activation in vitro

    NASA Astrophysics Data System (ADS)

    Bengal, Eyal; Flores, Osvaldo; Rangarajan, Pundi N.; Chen, Amy; Weintraub, Harold; Verma, Inder M.

    1994-06-01

    An in vitro transcription system from HeLa cells has been established in which MyoD and E47 proteins activate transcription both as homodimers and heterodimers. However, heterodimers activate transcription more efficiently than homodimers, and function synergistically from multiple binding sites. Positive control mutants in the basic region of MyoD that have previously been shown to be defective in initiating the myogenic program, can bind DNA but have lost their ability to function as transcriptional activators in vitro. Additionally, positive control mutants, unlike wild-type MyoD, fail to bind cooperatively to DNA. We propose that binding of MyoD complexes to high affinity MyoD binding sites induces conformational changes that facilitate cooperative binding to multiple sites and promote transcriptional activation.

  18. The Role of the Engineered Barrier System in Safety Cases for Geological Radioactive Waste Repoitories: An NEA Initiaive in Co-Operations with the EC, Process Issues and Modeling

    SciTech Connect

    D.G. Bennett; A.J. Hooper; S. Voinis; H. Umeki; A.V. Luik; J. Alonso

    2006-02-07

    The Integration Group for the Safety Case (IGSC) of the Nuclear Energy Agency (NEA) Radioactive Waste Management Committee in co-operation with the European Commission (EC) is conducting a project to develop a greater understanding of how to achieve the necessary integration for successful design, construction, testing, modeling, and assessment of engineered barrier systems. The project also seeks to clarify the role that the EBS plays in assuring the overall safety of a repository. A framework for the EBS Project is provided by a series of workshops that allow discussion of the wide range of activities necessary for the design, assessment and optimization of the EBS, and the integration of this information into the safety case. The topics of this series of workshops have been planned so that the EBS project will work progressively through the main aspects comprising one cycle of the design and optimization process. This paper seeks to communicate key results from the EBS project to a wider audience. The paper focuses on two topics discussed at the workshops: process issues and the role of modeling.

  19. Identification of the conserved spatial position of key active-site atoms in glycoside hydrolase 13 family members.

    PubMed

    Kumar, Vikash

    2010-07-19

    A computational study on the glycoside hydrolase 13 (GH13) family of the CAZy database has been carried out at the atomic level in order to identify the conserved positions that may be responsible for recognition of the substrate. Analysis with substrate analog-, inhibitor-, or product-bound 3D structures was carried out to find the atomic spatial arrangement of the amino acids that make -2, -1, +1, and +2 subsites and water oxygen atoms around the ligand. The identified conserved positions of subsites were independent from the nature of the amino acid. The -1 and +1 subsites have more conserved positions than the -2 and +2 subsites. Some of the clusters of the -1 and +1 subsites have atoms of the same chemical nature. A spatially conserved position for water, which is stabilized by a hydrogen bond with the carboxyl group of a proton donor (Glu) and Asp of the catalytic triad, was found in the -1 subsite of 75% of the enzymes subjected to analysis. This position could be the region of hydrolytic water. PMID:20557875

  20. South Asian co-operation in population education. Materials jointly developed for common use by South Asian population education programmes.

    PubMed

    1992-01-01

    Southern Asian population education programs have developed common materials on population and family life education. Countries involved were Bangladesh, India, Nepal, Pakistan, and Sri Lanka. The development of materials occurred as a byproduct of workshop conducted in Nepal from December 3-7, 1990 and December 2-10, 1991 in Sri Lanka. The 1st meeting was organized by UNESCO's Population Education Advisory team, and 6 curriculum topics were identified. Pretesting of materials was conducted between meetings. The final product was a set of 10 posters and 2 comic strips on the quality of life developed by India for elementary level use; a family life and sex education syllabus developed by Sri Lanka for secondary school use; 5 modules with teacher's guides and sample lessons for secondary school use; 5 modules and a teacher's guide on transmission of values on population education by Pakistan; 25 flip charts on maternal and child health for illiterates developed by Nepal; and a field guide on environmental protection for nonformal field workers developed by Bangladesh. Materials were designed through brainstorming sessions, designing of materials by experts, review by other groups, and retesting on target audiences. Revision followed pretesting. The plan for assuring use of materials was to have UNESCO print prototypes and then participants would seek financial support for country supplies. A suggestion was made to leave ample space for insertion of local language captions. Another suggestion was that the cartoon strip "Girls are Pearls" be printed on students' exercise books for all member countries. Member countries should also have available selected materials translated into English and distributed. UNESCO should continue to play the role of facilitator of information and expertise exchange among member countries. Another mutually cooperative activity was the Group Training Course on Population Education for the South Asian subregion held in December 1991. PMID

  1. Active beam position stabilization of pulsed lasers for long-distance ion profile diagnostics at the Spallation Neutron Source (SNS)

    SciTech Connect

    Hardin, Robert A; Liu, Yun; Long, Cary D; Aleksandrov, Alexander V; Blokland, Willem

    2011-01-01

    A high peak-power Q-switched laser has been used to monitor the ion beam profiles in the superconducting linac at the Spallation Neutron Source (SNS). The laser beam suffers from position drift due to movement, vibration, or thermal effects on the optical components in the 250-meter long laser beam transport line. We have designed, bench-tested, and implemented a beam position stabilization system by using an Ethernet CMOS camera, computer image processing and analysis, and a piezo-driven mirror platform. The system can respond at frequencies up to 30 Hz with a high position detection accuracy. With the beam stabilization system, we have achieved a laser beam pointing stability within a range of 2 rad (horizontal) to 4 rad (vertical), corresponding to beam drifts of only 0.5 mm 1 mm at the furthest measurement station located 250 meters away from the light source.

  2. In vitro activity of tedizolid against gram-positive bacteria in patients with skin and skin structure infections and hospital-acquired pneumonia: a Korean multicenter study.

    PubMed

    Lee, Yangsoon; Hong, Sung Kuk; Choi, Sunghak; Im, Weonbin; Yong, Dongeun; Lee, Kyungwon

    2015-09-01

    We compared the activities of tedizolid to those of linezolid and other commonly used antimicrobial agents against gram-positive cocci recovered from patients with skin and skin structure infections (SSSIs) and hospital-acquired pneumonia (HAP) in Korean hospitals. Gram-positive isolates were collected from 356 patients with SSSIs and 144 patients with HAP at eight hospitals in Korea from 2011 to 2014. SSSIs included impetigo, cellulitis, erysipelas, furuncles, abscesses, and infected burns. Antimicrobial susceptibility was tested by using the CLSI agar dilution method. All of the gram-positive isolates were inhibited by ≤1 μg/mL tedizolid. The minimum inhibitory concentration [MIC]₉₀ of tedizolid was 0.5 μg/mL for methicillin-resistant Staphylococcus aureus, which was 4-fold lower than that of linezolid. Tedizolid may become a useful option for the treatment of SSSIs and HAP caused by gram-positive bacteria. PMID:26206690

  3. Characterization of a multi-user indoor positioning system based on low cost depth vision (Kinect) for monitoring human activity in a smart home.

    PubMed

    Sevrin, Loïc; Noury, Norbert; Abouchi, Nacer; Jumel, Fabrice; Massot, Bertrand; Saraydaryan, Jacques

    2015-01-01

    An increasing number of systems use indoor positioning for many scenarios such as asset tracking, health care, games, manufacturing, logistics, shopping, and security. Many technologies are available and the use of depth cameras is becoming more and more attractive as this kind of device becomes affordable and easy to handle. This paper contributes to the effort of creating an indoor positioning system based on low cost depth cameras (Kinect). A method is proposed to optimize the calibration of the depth cameras, to describe the multi-camera data fusion and to specify a global positioning projection to maintain the compatibility with outdoor positioning systems. The monitoring of the people trajectories at home is intended for the early detection of a shift in daily activities which highlights disabilities and loss of autonomy. This system is meant to improve homecare health management at home for a better end of life at a sustainable cost for the community. PMID:26737415

  4. The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds.

    PubMed

    Mpima, Sheila; Ohnmacht, Stephan A; Barletta, Maria; Husby, Jarmila; Pett, Luke C; Gunaratnam, Mekala; Hilton, Stephen T; Neidle, Stephen

    2013-10-15

    The synthesis together with biophysical and biological evaluation of a series of tetra-substituted naphthalene diimide (ND) compounds, are presented. These compounds are positional isomers of a recently-described series of quadruplex-binding ND derivatives, in which the two N-methyl-piperidine-alkyl side-chains have now been interchanged with the positions of side-chains bearing a range of end-groups. Molecular dynamics simulations of a pair of positional isomers are in accord with the quadruplex stabilization and biological data for these compounds. Analysis of structure-activity data indicates that for compounds where the side-chains are not of equivalent length then the positional isomers described here tend to have improved cell proliferation potency and in some instances, superior quadruplex stabilization ability. PMID:23769166

  5. Exercise motives and positive body image in physically active college women and men: Exploring an expanded acceptance model of intuitive eating.

    PubMed

    Tylka, Tracy L; Homan, Kristin J

    2015-09-01

    The acceptance model of intuitive eating posits that body acceptance by others facilitates body appreciation and internal body orientation, which contribute to intuitive eating. Two domains of exercise motives (functional and appearance) may also be linked to these variables, and thus were integrated into the model. The model fit the data well for 406 physically active U.S. college students, although some pathways were stronger for women. Body acceptance by others directly contributed to higher functional exercise motives and indirectly contributed to lower appearance exercise motives through higher internal body orientation. Functional exercise motives positively, and appearance exercise motives inversely, contributed to body appreciation. Whereas body appreciation positively, and appearance exercise motives inversely, contributed to intuitive eating for women, only the latter association was evident for men. To benefit positive body image and intuitive eating, efforts should encourage body acceptance by others and emphasize functional and de-emphasize appearance exercise motives. PMID:26281958

  6. Correlates of Long-Term Participation in a Physical Activity-Based Positive Youth Development Program for Low-Income Youth: Sustained Involvement and Psychosocial Outcomes

    ERIC Educational Resources Information Center

    Ullrich-French, Sarah; McDonough, Meghan H.

    2013-01-01

    This study examined correlates of long-term participation in a positive youth development (PYD) program. Low-income youth (N = 215) age 8-13 of diverse ethnicity participating in a summer physical activity-based PYD program completed questionnaires at the beginning and end of the program (year 1) and at the beginning of year 2. Those with lower…

  7. A poultry-intestinal isolate of Campylobacter jejuni produces a bacteriocin (CUV-3) active against a range of Gram positive bacterial pathogens including Clostridium perfringens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly isolated bacteriocin, CUV-3, produced by a poultry cecal isolate of Campylobacter jejuni strain CUV-3 had inhibitory activity against several Gram positive bacteria including Clostridium perfringens (38 strains), Staphylococcus aureus, Staph.epidermidis and Listeria monocytogenes. The pept...

  8. College/University Physical Activity Instruction Programs: A Critical Piece in the Education of Young Adults. A Position Paper from the National Association for Sport and Physical Education

    ERIC Educational Resources Information Center

    American Alliance for Health, Physical Education, Recreation and Dance (NJ1), 2007

    2007-01-01

    It is the position of the National Association of Sport and Physical Education (NASPE) and the College and University Physical Education Council (CUPEC) that all colleges and universities uphold a physical activity instructional program for students as a strong and integral part of the academic curriculum. Bombarded by popular culture, newfound…

  9. The Effects of Aesthetic Science Activities on Improving At-Risk Families Children's Anxiety about Learning Science and Positive Thinking

    ERIC Educational Resources Information Center

    Hong, Zuway-R.; Lin, Huann-Shyang; Chen, Hsiang-Ting; Wang, Hsin-Hui; Lin, Chia-Jung

    2014-01-01

    The purpose of this study was to explore the effects of aesthetic science activities on improving elementary school at-risk families' children's positive thinking, attitudes toward science, and decreasing their anxiety about learning science. Thirty-six 4th-grade children from at-risk families volunteered to participate in a 12-week…

  10. Unveiling hidden catalytic contributions of the conserved His/Trp-III in tyrosine recombinases: assembly of a novel active site in Flp recombinase harboring alanine at this position

    PubMed Central

    Ma, Chien-Hui; Kwiatek, Agnieszka; Bolusani, Swetha; Voziyanov, Yuri; Jayaram, Makkuni

    2007-01-01

    Summary The catalytic pentad of tyrosine recombinases, that assists the tyrosine nucleophile, includes a conserved histidine/tryptophan (His/Trp-III). Flp and Cre harbor tryptophan at this position; most of their kin recombinases display histidine. Contrary to the conservation rule, Flp(W330F) is a much stronger recombinase than Flp(W330H). The hydrophobicity of Trp-330 or Phe-330 is utilized in correctly positioning Tyr-343 during the strand cleavage step of recombination. Why then is phenylalanine almost never encountered in the recombinase family at this conserved position? Using exogenous nucleophiles and synthetic methylphosphonate or 5'-thiolate substrates, we decipher that Trp-330 also assists in the activation of the scissile phosphate and the departure of the 5'-hydroxyl leaving group. These two functions are consistent with the hydrogen bonding property of Trp-330 as well as its location in structures of the Flp recombination complexes. However, van der Waals contact between Trp-330 and Arg-308 may also be important for the phosphate activation step. A structure based suppression strategy permits the inactive variant Flp(W330A) to be rescued by a second site mutation A339M. Modeling alanine and methionine at positions 330 and 339, respectively, in the Flp crystal structure suggests a plausible mechanism for active site restoration. Successful suppression suggests the possibility of evolving, by design, new active site configurations for tyrosine recombination. PMID:17367810

  11. Assisting People with Multiple Disabilities by Actively Keeping the Head in an Upright Position with a Nintendo Wii Remote Controller through the Control of an Environmental Stimulation

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Shih, Chia-Ju; Shih, Ching-Tien

    2011-01-01

    The latest researches have adopted software technology by applying the Nintendo Wii Remote Controller to the correction of hyperactive limb behavior. This study extended Wii Remote Controller functionality for improper head position (posture) correction (i.e. actively adjusting abnormal head posture) to assess whether two people with multiple…

  12. The DNA-binding domain of the transcriptional activator protein NifA resides in its carboxy terminus, recognises the upstream activator sequences of nif promoters and can be separated from the positive control function of NifA.

    PubMed Central

    Morett, E; Cannon, W; Buck, M

    1988-01-01

    The positive control protein NifA activates transcription of nitrogen fixation promoters in Klebsiella pneumoniae. NifA is believed to bind to specific sites, the upstream activator sequences (UAS's), of the nif promoters which it activates. We have now shown by mutation of the carboxy terminus of NifA that this is the DNA-binding domain and that the DNA-binding and positive activator functions of NifA can be separated. Mutational analysis of the nifH UAS and in vivo methylation protection analysis of the interaction of NifA with the nifH promoter demonstrates that the UAS is recognised by the carboxy terminus of NifA. The UAS's of K. pneumoniae nif promoters are also required for activation by the Rhizobium meliloti NifA indicating that this activator also possesses DNA-binding activity. Images PMID:3062575

  13. Anti-signal recognition particle antibody-positive polymyositis in a patient with Sjögren's syndrome showing various types of annular erythema: Positive correlation between the activities of annular erythema and myositis.

    PubMed

    Kabuto, Miho; Fujimoto, Noriki; Hamaguchi, Yasuhito; Tanaka, Toshihiro

    2016-08-01

    Annular erythema with Sjögren's syndrome (AESS) is occasionally found, especially in Asian patients, which is classified into three types. We present a case of Sjögren's syndrome showing various types of AESS with anti-signal recognition particle antibody-positive polymyositis. We successfully treated the eruption and myositis with a low dose of prednisolone. Every onset of annular erythema coincided with elevation of serum creatine kinase levels, which suggests the correlation between the activities of annular erythema and polymyositis. PMID:26972113

  14. Hui Malama O Ke Kai: A Positive Prevention-Based Youth Development Program Based on Native Hawaiian Values and Activities

    ERIC Educational Resources Information Center

    Hishinuma, Earl S.; Chang, Janice Y.; Sy, Angela; Greaney, Malia F.; Morris, Katherine A.; Scronce, Ami C.; Rehuher, Davis; Nishimura, Stephanie T.

    2009-01-01

    Evaluation of after-school programs that are culturally and place-based and promote positive youth development among minority and indigenous youths has not been widely published. The present evaluation is the first of its kind of an after-school, youth-risk prevention program called Hui Malama O Ke Kai (HMK), that emphasizes Native Hawaiian values…

  15. Food reward without a timing component does not alter the timing of activity under positive energy balance.

    PubMed

    van der Vinne, V; Akkerman, J; Lanting, G D; Riede, S J; Hut, R A

    2015-09-24

    Circadian clocks drive daily rhythms in physiology and behavior which allow organisms to anticipate predictable daily changes in the environment. In most mammals, circadian rhythms result in nocturnal activity patterns although plasticity of the circadian system allows activity patterns to shift to different times of day. Such plasticity is seen when food access is restricted to a few hours during the resting (light) phase resulting in food anticipatory activity (FAA) in the hours preceding food availability. The mechanisms underlying FAA are unknown but data suggest the involvement of the reward system and homeostatic regulation of metabolism. We previously demonstrated the isolated effect of metabolism by inducing diurnality in response to energetic challenges. Here the importance of reward timing in inducing daytime activity is assessed. The daily activity distribution of mice earning palatable chocolate at their preferred time by working in a running wheel was compared with that of mice receiving a timed palatable meal at noon. Mice working for chocolate (WFC) without being energetically challenged increased their total daily activity but this did not result in a shift to diurnality. Providing a chocolate meal at noon each day increased daytime activity, identifying food timing as a factor capable of altering the daily distribution of activity and rest. These results show that timing of food reward and energetic challenges are both independently sufficient to induce diurnality in nocturnal mammals. FAA observed following timed food restriction is likely the result of an additive effect of distinct regulatory pathways activated by energetic challenges and food reward. PMID:26215921

  16. A Position Statement from the National Association for Sport and Physical Education: Comprehensive School Physical Activity Program

    ERIC Educational Resources Information Center

    Strategies: A Journal for Physical and Sport Educators, 2008

    2008-01-01

    Schools play an important role in public health, and the physical, mental, and social benefits of regular physical activity for youth are well documented. Leading public health, medical, and educational organizations have made important physical activity recommendations for school-aged youth. The National Association for Sport and Physical …

  17. Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria.

    PubMed

    Torcato, Inês M; Huang, Yen-Hua; Franquelim, Henri G; Gaspar, Diana; Craik, David J; Castanho, Miguel A R B; Troeira Henriques, Sónia

    2013-03-01

    BP100 is a short cationic antimicrobial peptide with a mechanism of action dependent on peptide-lipid interactions and microbial surface charge neutralization. Although active against Gram-negative bacteria, BP100 is inactive against Gram-positive bacteria. In this study we report two newly designed BP100 analogues, RW-BP100 and R-BP100 that have the Tyr residue replaced with a Trp and/or the Lys residues replaced with an Arg. The new analogues in addition to being active against Gram-negative bacteria, possess activity against all tested Gram-positive bacteria. Mechanistic studies using atomic force microscopy, surface plasmon resonance and fluorescence methodologies reveal that the antibacterial efficiency follows the affinity for bacterial membrane. The studies suggest that the activity of BP100 and its analogues against Gram-negative bacteria is mainly driven by electrostatic interactions with the lipopolysaccharide layer and is followed by binding to and disruption of the inner membrane, whereas activity against Gram-positive bacteria, in addition to electrostatic attraction to the exposed lipoteichoic acids, requires an ability to more deeply insert in the membrane environment, which is favoured with Arg residues and is facilitated in the presence of a Trp residue. Knowledge on the mechanism of action of these antimicrobial peptides provides information that assists in the design of antimicrobials with higher efficacy and broader spectra of action, but also on the design of peptides with higher specificity if required. PMID:23246973

  18. Decreased entropy of symbolic heart rate dynamics during daily activity as a predictor of positive head-up tilt test in patients with alleged neurocardiogenic syncope

    NASA Astrophysics Data System (ADS)

    Kim, June-Soo; Park, Jeong-Euy; Seo, Jung-Don; Lee, Won-Ro; Kim, Hee-Soo; Noh, Jung-Il; Kim, Nam-Su; Yum, Myung-Kul

    2000-11-01

    Entropy measures of RR interval variability during daily activity over a 24 h period were compared in 30 patients with a positive head-up tilt (HUT) test and 30 patients with a negative HUT test who had a history of alleged neurocardiogenic syncope. Two different entropies, approximate entropy (ApEn) and entropy of symbolic dynamics (SymEn), were employed. In patients showing a positive HUT test, the entropies were significantly decreased when compared with the patients with a negative HUT test. In addition, SymEn in the patients with a negative HUT test was significantly lower than in the normal controls. Discriminant analysis using SymEn could correctly identify 89.3% (520/582) of the 1 h RR interval data of the patients with a positive HUT test regardless of the time of day. Baseline entropies of heart rate dynamics during daily activity were found to be significantly lower in patients with alleged neurocardiogenic syncope and a positive HUT test than in those with the same history but with a negative HUT test. The decreased entropy of symbolic heart rate dynamics may be of predictive value of a positive HUT test in patients with alleged neurocardiogenic syncope.

  19. Visual feedback of the non-moving limb improves active joint-position sense of the impaired limb in Spastic Hemiparetic Cerebral Palsy.

    PubMed

    Smorenburg, Ana R P; Ledebt, Annick; Deconinck, Frederik J A; Savelsbergh, Geert J P

    2011-01-01

    This study examined the active joint-position sense in children with Spastic Hemiparetic Cerebral Palsy (SHCP) and the effect of static visual feedback and static mirror visual feedback, of the non-moving limb, on the joint-position sense. Participants were asked to match the position of one upper limb with that of the contralateral limb. The task was performed in three visual conditions: without visual feedback (no vision); with visual feedback of the non-moving limb (screen); and with visual feedback of the non-moving limb and its mirror reflection (mirror). In addition to the proprioceptive measure, a functional test [Quality of Upper Extremity Skills Test (QUEST)] was performed and the amount of spasticity was determined in order to examine their relation with proprioceptive ability. The accuracy of matching was significantly influenced by the distance that had to be covered by the matching limb; a larger distance resulted in a lower matching accuracy. Moreover it was demonstrated that static (mirror) visual feedback improved the matching accuracy. A clear relation between functionality, as measured by the QUEST, and active joint-position sense was not found. This might be explained by the availability of visual information during the performance of the QUEST. It is concluded that static visual feedback improves matching accuracy in children with SHCP and that the initial distance between the limbs is an influential factor which has to be taken into account when measuring joint-position sense. PMID:21306868

  20. Low-crystalline β-FeOOH and vanadium ferrite for positive active materials of lithium secondary cells

    NASA Astrophysics Data System (ADS)

    Funabiki, Atsushi; Yasuda, Hideo; Yamachi, Masanori

    Low-crystalline β-FeOOH and vanadium ferrite were prepared by a simple hydrolysis method. XRD measurement revealed that the former material had a framework of β-FeOOH with somewhat amorphous structure, and that the latter one gave a crystalline structure analogous to that of the hydrated iron orthovanadate. From the electrochemical measurements, it was found that the low-crystalline β-FeOOH positive electrode showed a discharge capacity of 230 mAh/g in the potential range of 4.3 V and 1.6 V versus Li/Li +, and better cycle performance than the high-crystalline one. The vanadium ferrite positive electrode also showed a high discharge capacity over 300 mAh/g and superior cycle performance.