Science.gov

Sample records for positive co-operative activity

  1. The PRISM data/model co-operative: current modelling activities, future plans and data requirements

    NASA Astrophysics Data System (ADS)

    Haywood, Alan

    2010-05-01

    Here we review current activities and future model and data requirements associated with the palaeoclimate modelling arm of the PRISM data/model co-operative. The talk will begin with a description of modelling focussed on understanding the behaviour of climate phenomena that are responsible for generating significant regional decadal and sub-decadal climate variability (ENSO and NAO), and the challenges associated with linking such predictions to mid-Piacenzian palaeoenvironmental data. Secondly, we will examine current efforts to understand the role of changing sea-surface temperatures, in relation to other important boundary conditions, in driving global and regional climate/environmental shifts recognised in the proxy data. Thirdly, we will examine initial results from coupled climate and ice sheet modelling examining the response of the Greenland and East Antarctic Ice Sheets to orbital variations and how these predicted changes relate to current estimates of mid-Piacenzian mean sea level and sea level variability. Our future plans centre on (a) the development of the Pliocene Model Intercomparison Project, (b) understanding uncertainty in climate model predictions of mid-Piacenzian climates and (c) moving towards an Earth System Modelling framework for the PRISM interval. With the 4th iteration of the PRISM palaeoenvironmental data set under construction we briefly outline how the demands of modern climate and earth system models will partly shape PRISM4, as well as the new scientific opportunities that will stem from it (e.g. the advent of isotope enabled models, higher resolution boundary conditions, river routing schemes and palaeobathymetry).

  2. The significance of abrupt transitions in Lineweaver-Burk plots with particular reference to glutamate dehydrogenase. Negative and positive co-operativity in catalytic rate constants.

    PubMed

    Engel, P C; Ferdinand, W

    1973-01-01

    1. Lineweaver-Burk plots for glutamate dehydrogenase, glucose 6-phosphate dehydrogenase and several other enzymes show one or more abrupt transitions between apparently linear sections. These transitions correspond to abrupt increases in the apparent K(m) and V(max.) with increasing concentration of the varied substrate. 2. The generalized reciprocal initial-rate equation for a multi-site enzyme requires several restrictions to be put on it in order to generate such plots. These mathematical conditions are explored. 3. It is shown that the effective omission of a term in the denominator of the reciprocal initial-rate equation represents a minimal requirement for generation of abrupt transitions. This corresponds in physical terms to negative co-operativity followed by positive co-operativity affecting the catalytic rate constant for the reaction. 4. Previous models for glutamate dehydrogenase cannot adequately account for the results. On the other hand, the model based on both negative and positive co-operativity gives a good fit to the experimental points. 5. The conclusions are discussed in relation to current knowledge of the structure and mechanism of glutamate dehydrogenase.

  3. A zinc-dependent DNA-binding activity co-operates with cAMP-responsive-element-binding protein to activate the human thyroglobulin enhancer.

    PubMed Central

    Berg, V; Vassart, G; Christophe, D

    1997-01-01

    Footprinting experiments involving the human thyroglobulin gene enhancer and thyroid nuclear extracts revealed a protected region called X2, containing an incomplete cAMP-responsive element (CRE). Band-shift experiments identified two binding activities recognizing the X2 element: a CRE-binding protein (CREB)/activating transcription factor (ATF) relative that binds the half CRE motif and a second factor that interacts with a G-rich motif located just upstream from the CRE. The first factor appears to be CREB itself, as indicated by the supershifting when using an antibody directed against CREB, and the second DNA-binding activity involved was shown to be zinc-dependent and exhibited an apparent molecular mass of 42-44 kDa in South-Western blotting experiments. This factor may represent a novel entity, which we named CAF, for 'CREB Associated Factor'. Three copies of X2 sequence conferred a strong cAMP-dependent transcriptional activation to a heterologous promoter in transient transfection assay in cAMP-stimulated primary thyrocytes and HeLa cells. Transfection experiments of constructs containing the X2 element mutated in either the CRE or the G-rich site showed that both motifs were required for this transcription activating function. Moreover, the combination of several individual X2 elements mutated in either the CRE or the G-rich motif did not exhibit full transcriptional activity. This suggests that, in the context of the X2 element, CREB requires a close interaction with CAF to achieve both basal and cAMP-dependent transcriptional activation. PMID:9163323

  4. 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…

  5. 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…

  6. 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…

  7. Reasons to Co-Operate: Co-Operative Solutions for Schools

    ERIC Educational Resources Information Center

    Roach, Patrick

    2013-01-01

    The NASUWT's landmark agreement with the Schools Co-operative Society has provided a new spur to co-operation, collaboration and collegiality in schools. Against a background of rapid and radical changes to the education landscape, co-operative schools are viewed by many as a means to maintaining public service ethos and values in education. The…

  8. 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.

  9. 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.

  10. 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…

  11. 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.

  12. Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding.

    PubMed

    Chang, J F; Phillips, K; Lundbäck, T; Gstaiger, M; Ladbury, J E; Luisi, B

    1999-05-21

    The expression of immunoglobulin genes is controlled in part by the DNA-binding protein Oct-1 and the B cell-specific transcription co-activator, Bob1 (also known as OCA-B or OBF-1) that together form a complex on the Igkappa promoter. We have characterised the assembly of the ternary complex using biophysical methods. Bob1 binds specifically as a monomer to the complex of the Oct-1 DNA-binding domain (Oct-1 POU) and the Igkappa promoter, but binds weakly to either Oct-1 POU or the Igkappa promoter alone, indicating that both are required to make an avid complex. Ternary complex formation requires a defined DNA sequence, as the stability of the complex can be strongly affected by a single base-pair change or by removing 5-methyl groups from selected thymine bases.In isolation, Bob1 appears to have little secondary structure, but may become partially structured upon recruitment into the ternary complex as demonstrated by circular dichroism spectra and calorimetry. These and other findings suggest that ternary complex formation requires a defined geometry of the POU/DNA complex, and that the co-activator makes stereo-specific contacts to both the POU protein and the major groove of the DNA that induces its fold.

  13. 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…

  14. 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

  15. 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

    2015-06-08

    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.

  16. 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…

  17. 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…

  18. 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.

  19. 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.

  20. Hormone activation induces nucleosome positioning in vivo

    PubMed Central

    Belikov, Sergey; Gelius, Birgitta; Almouzni, Geneviève; Wrange, Örjan

    2000-01-01

    The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone. PMID:10698943

  1. 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.

  2. 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…

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

    PubMed

    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.

  4. 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.

  5. 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…

  6. Impact of Co-Operative Learning Strategies in English

    ERIC Educational Resources Information Center

    Singaravelu, G.

    2010-01-01

    The study illuminates the effectiveness of Co-operative Learning Strategies in learning English Grammar for the learners at secondary level. Cooperative Learning is particularly beneficial for any student learning as a second language. It promotes peer interaction, which helps the development of language and the learning of concepts with content.…

  7. 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…

  8. 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

  9. Evidence for co-operativity in coenzyme binding to tetrameric Sulfolobus solfataricus alcohol dehydrogenase and its structural basis: fluorescence, kinetic and structural studies of the wild-type enzyme and non-co-operative N249Y mutant

    PubMed Central

    2005-01-01

    The interaction of coenzyme with thermostable homotetrameric NAD(H)-dependent alcohol dehydrogenase from the thermoacidophilic sulphur-dependent crenarchaeon Sulfolobus solfataricus (SsADH) and its N249Y (Asn-249→Tyr) mutant was studied using the high fluorescence sensitivity of its tryptophan residues Trp-95 and Trp-117 to the binding of coenzyme moieties. Fluorescence quenching studies performed at 25 °C show that SsADH exhibits linearity in the NAD(H) binding [the Hill coefficient (h)∼1) at pH 9.8 and at moderate ionic strength, in addition to positive co-operativity (h=2.0–2.4) at pH 7.8 and 6.8, and at pH 9.8 in the presence of salt. Furthermore, NADH binding is positively co-operative below 20 °C (h∼3) and negatively co-operative at 40–50 °C (h∼0.7), as determined at moderate ionic strength and pH 9.8. Steady-state kinetic measurements show that SsADH displays standard Michaelis–Menten kinetics between 35 and 45 °C, but exhibits positive and negative co-operativity for NADH oxidation below (h=3.3 at 20 °C) and above (h=0.7 at 70–80 °C) this range of temperatures respectively. However, N249Y SsADH displays non-co-operative behaviour in coenzyme binding under the same experimental conditions used for the wild-type enzyme. In loop 270–275 of the coenzyme domain and segments at the interface of dimer A–B, analyses of the wild-type and mutant SsADH structures identified the structural elements involved in the intersubunit communication and suggested a possible structural basis for co-operativity. This is the first report of co-operativity in a tetrameric ADH and of temperature-induced co-operativity in a thermophilic enzyme. PMID:15651978

  10. 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

  11. Criteria for Formation of Active Personal Position of Schoolchildren

    ERIC Educational Resources Information Center

    Kunanbayeva, Magziya Sh.

    2016-01-01

    The article considers the problem and the importance of formation of the active personal position of schoolchildren. Active personal position is a complex concept, which includes the ability to a problem solution, the ability to work in a team, the ability to express his or her views. The formation of an active personal position at school is…

  12. Healthcare technology co-operatives: Innovative about innovation.

    PubMed

    Heron, Nicola M; Tindale, Wendy B

    2014-01-01

    The paper provides an introduction to the National Institute for Health Research Devices for Dignity Healthcare Technology Co-operative. Embedded within the NHS, Devices for Dignity identifies areas of unmet clinical need and translates these into research and development projects to develop new medical technologies. It addresses the needs of people living with long-term conditions, helping them to live more dignified and independent lives. Through partnerships with patients, universities, the NHS and industry, Devices for Dignity has developed an innovation methodology for successful medical technology innovation.

  13. 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,…

  14. An Effect of the Co-Operative Network Model for Students' Quality in Thai Primary Schools

    ERIC Educational Resources Information Center

    Khanthaphum, Udomsin; Tesaputa, Kowat; Weangsamoot, Visoot

    2016-01-01

    This research aimed: 1) to study the current and desirable states of the co-operative network in developing the learners' quality in Thai primary schools, 2) to develop a model of the co-operative network in developing the learners' quality, and 3) to examine the results of implementation of the co-operative network model in the primary school.…

  15. 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 group…

  16. Fragile phagocytes: FMRP positively regulates engulfment activity.

    PubMed

    Logan, Mary A

    2017-03-06

    Defective immune system function is implicated in autism spectrum disorders, including Fragile X syndrome. In this issue, O'Connor et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607093) demonstrate that phagocytic activity of systemic immune cells is compromised in a Drosophila melanogaster model of Fragile X, highlighting intriguing new mechanistic connections between FMRP, innate immunity, and abnormal development.

  17. A voice from the high wire: Public involvement in a co-operative siting process

    SciTech Connect

    Oates, D.J.L.

    1995-05-01

    The author is a public consultation and communications consultant to the Siting Task Force (STF), Low level Radioactive Waste Management. The STF is a Canadian government-appointed yet independent body implementing a voluntary, co-operative siting process for a long term storage or disposal facility for 1 million cubic metres of LLRW. The presentation will document the experiences of and lessons learned by the author during her role developing and implementing a public involvement program for the process. The Co-operative Siting Process is a new approach to siting controversial facilities. It is based on the belief that communities should accept such a facility in their backyard and not be forced against their will on technical or political grounds. A formal `ground rules-up-front` process was developed and is now being carried out, with completion slated for April, 1995. Putting these rules and theories into practice has resulted in significant changes being made to the work plan for technical activities, and in a sober second look at the intricacies involved in planning and carrying out a thorough and efficient public involvement program that remain practical and cost-effective. There is a delicate balancing act between meaningful public participation that lays the foundation for trust, confidence and consensus, and public involvement that can result in the process being side-tracked and legitimate solutions and technical activities becoming mired in political and personal agendas.

  18. Maternal-fetal resource allocation: co-operation and conflict.

    PubMed

    Fowden, A L; Moore, T

    2012-11-01

    Pregnancy is generally a co-operative interaction between mother and fetus in which the evolutionary genetic interests of both benefit from production of healthy offspring. While this view is largely supported by empirical data, Kinship Theory predicts that mother and fetus will disagree over the optimum level of maternal investment that maximises their respective fitnesses. This conflict will be more evident with polyandrous than monogamous mating systems, when resources are scarce and in late gestation when the fetus is growing maximally, particularly if conceptus mass is large relative to maternal mass. As the site of nutrient transfer, the placenta is pivotal in the tug-of-war between mother and fetus over resource allocation. It responds to both fetal signals of nutrient demand and maternal signals of nutrient availability and, by adapting its phenotype, regulates the distribution of available resources. These adaptations involve changes in placental size, morphology, transport characteristics, metabolism and hormone bioavailability. They are mediated by key growth regulatory, endocrine and nutrient supply genes responsive to mismatches between nutrient availability and the fetal genetic drive for growth. Indeed, evolution of genomic imprinting and placental secretion of hormones are believed to have been driven by maternal-fetal conflict over resource allocation. Although many of the specific mechanisms involved still have to be identified, the placenta confers optimal fitness on the offspring for its developmental environment by balancing conflict and cooperation in the allocation of resources through generation of nutrient transport phenotypes specific to the prevailing nutritional conditions and/or fetal genotype.

  19. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    PubMed

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  20. 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)

  1. 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…

  2. Laser optical disk position encoder with active heads

    NASA Technical Reports Server (NTRS)

    Osborne, Eric P.

    1991-01-01

    An angular position encoder that minimizes the effects of eccentricity and other misalignments between the disk and the read stations by employing heads with beam steering optics that actively track the disk in directions along the disk radius and normal to its surface is discussed. The device adapts features prevalent in optical disk technology to the application of angular position sensing.

  3. '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

  4. 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.

  5. 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…

  6. 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…

  7. 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.

  8. Analysis of the co-operative interaction between the allosterically regulated proteins GK and GKRP using tryptophan fluorescence

    PubMed Central

    Zelent, Bogumil; Raimondo, Anne; Barrett, Amy; Buettger, Carol W.; Chen, Pan; Gloyn, Anna L.; Matschinsky, Franz M.

    2014-01-01

    Hepatic glucose phosphorylation by GK (glucokinase) is regulated by GKRP (GK regulatory protein). GKRP forms a cytosolic complex with GK followed by nuclear import and storage, leading to inhibition of GK activity. This process is initiated by low glucose, but reversed nutritionally by high glucose and fructose or pharmacologically by GKAs (GK activators) and GKRPIs (GKRP inhibitors). To study the regulation of this process by glucose, fructose-phosphate esters and a GKA, we measured the TF (tryptophan fluorescence) of human WT (wild-type) and GKRP-P446L (a mutation associated with high serum triacylglycerol) in the presence of non-fluorescent GK with its tryptophan residues mutated. Titration of GKRP-WT by GK resulted in a sigmoidal increase in TF, suggesting co-operative PPIs (protein–protein interactions) perhaps due to the hysteretic nature of GK. The affinity of GK for GKRP was decreased and binding co-operativity increased by glucose, fructose 1-phosphate and GKA, reflecting disruption of the GK–GKRP complex. Similar studies with GKRP-P446L showed significantly different results compared with GKRP-WT, suggesting impairment of complex formation and nuclear storage. The results of the present TF-based biophysical analysis of PPIs between GK and GKRP suggest that hepatic glucose metabolism is regulated by a metabolite-sensitive drug-responsive co-operative molecular switch, involving complex formation between these two allosterically regulated proteins. PMID:24568320

  9. [Hamburg model-project for minors who are at risk for sexual offending: co-operation between the institutions in Hamburg, Germany].

    PubMed

    Spehr, Aranke; Driemeyer, Wiebke; Briken, Peer

    2010-01-01

    When children and adolescents show deviant sexual behavior, co-operation between institutions of the youth welfare service is necessary in order to prevent further assaults. As a part of the Hamburg model project for minors who are at risk for sexual offending we evaluated the existing case-unspecific co-operation between the city's institutions. Selection of the sample resulted in a diagram of co-operation between institutions that have or might have contact to sexual deviant children or juveniles. By analyzing 147 online-surveys, comprising quantitative as well as qualitative questions, revealed a comprehensive system rich in resources but only little case-unspecific cooperation. Highest average rating in co-operation was given to the non-governmental institutions and the police. The inquiry of reasons for the co-operation indicated a demand for specialized diagnostics and advice. Positively evaluated were an efficient and fast processing, an unbureaucratic handling of the case and constant availability. Pointed out negatively were "not-reacting", trivializing and a lack of capacities. In order to improve the level of information and the range of intervention programs, training of professionals in school and the youth welfare service is needed.

  10. On the road towards better health gain through co-operation in the European Union?

    PubMed

    Schutyser, K

    1999-01-01

    Explained are some 4 paradoxes, amongst many others, in healthcare and hospital policy and the turbulent "changes" and so-called changes they are going through all over Europe:--change vs being changed?--cost vs investment?--compete vs co-operate?--patients vs healthcare workers? There is certainly not yet a politically explicit option for a comprehensive European (Union) healthcare system. The national governments explicitly want to keep their part of the social organisation of society in their own hands. But at the same time the EU is active in the healthcare field when exercising its (reduced) competencies in public health and in data comparison as well as when acting in its very broad domains of the internal market. The informative and benchmarking role of the EU is immense and it has huge means to stimulate European networks and scientific research even in healthcare systems and policymaking. A strong message here is certainly to correctly invest in real health gain for patients and society through co-operation and networking among the many stakeholders in health and healthcare. The challenge for the future, for the numerous actors on the very slippery slope of health is to keep upright as moderate consumers, producers and rulers. This appeal to moderation, i.e. to prevention of exaggeration, which comes down to an attitude of subsidiarity, is a general conclusion, which may seem idealistic. However, one can qualify it also as "2000 realism" which our western social healthcare systems need for surviving, as they will have to see to a more solidarity-based coverage of health risks instead of reserving healthcare to the rich, and as they will have to open their social quality systems even more throughout the world.

  11. Global positioning system: a new opportunity in physical activity measurement.

    PubMed

    Maddison, Ralph; Ni Mhurchu, Cliona

    2009-11-04

    Accurate measurement of physical activity is a pre-requisite to monitor population physical activity levels and design effective interventions. Global Positioning System (GPS) technology offers potential to improve the measurement of physical activity. This paper 1) reviews the extant literature on the application of GPS to monitor human movement, with a particular emphasis on free-living physical activity, 2) discusses issues associated with GPS use, and 3) provides recommendations for future research. Overall findings show that GPS is a useful tool to augment our understanding of physical activity by providing the context (location) of the activity and used together with Geographical Information Systems can provide some insight into how people interact with the environment. However, no studies have shown that GPS alone is a reliable and valid measure of physical activity.

  12. Global positioning system: a new opportunity in physical activity measurement

    PubMed Central

    Maddison, Ralph; Ni Mhurchu, Cliona

    2009-01-01

    Accurate measurement of physical activity is a pre-requisite to monitor population physical activity levels and design effective interventions. Global Positioning System (GPS) technology offers potential to improve the measurement of physical activity. This paper 1) reviews the extant literature on the application of GPS to monitor human movement, with a particular emphasis on free-living physical activity, 2) discusses issues associated with GPS use, and 3) provides recommendations for future research. Overall findings show that GPS is a useful tool to augment our understanding of physical activity by providing the context (location) of the activity and used together with Geographical Information Systems can provide some insight into how people interact with the environment. However, no studies have shown that GPS alone is a reliable and valid measure of physical activity. PMID:19887012

  13. 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

  14. 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.

  15. Co-operation in Environmental Education at the Tertiary Level in the Asia-Pacific Region.

    ERIC Educational Resources Information Center

    Sato, Masahisa; Bhandari, Bishnu; Abe, Osamu

    2001-01-01

    Analyzes the co-operation in environmental education at the tertiary level with regard to sub-regions, which include North-East Asia, South-East Asia, South Asia, and the South Pacific. (Contains 17 references.) (YDS)

  16. 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…

  17. 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…

  18. Positive Technology for Healthy Living and Active Ageing.

    PubMed

    Riva, Giuseppe; Gaggioli, Andrea; Villani, Daniela; Cipresso, Pietro; Repetto, Claudia; Serino, Silvia; Triberti, Stefano; Brivio, Eleonora; Galimberti, Carlo; Graffigna, Guendalina

    2014-01-01

    Information and communication technologies are widely and rapidly spreading in people's daily lives. But what is the possible role of the mass proliferation of digital devices in supporting healthy living and active ageing? Are they useful in fostering personal growth and individual integration of the elderly, by promoting satisfaction, opportunities for action, and self-expression? Rather, do they enhance automation, impose constraints on personal initiative, and result in compulsive consumption of information? In this chapter, we suggest that possible answers to these questions will be offered by the "Positive Technology" approach, i.e., the scientific and applied approach to using technology so that it improves the quality of our personal experiences through its structuring, augmentation, and/or replacement. First, we suggest that it is possible to use technology to manipulate the quality of experience with the goal of increasing wellness and generating strengths and resilience in individuals, organizations, and society. Then, we classify positive technologies according to their effects on these three features of personal experience - Hedonic: technologies used to induce positive and pleasant experiences; Eudaimonic: technologies used to support individuals in reaching engaging and self-actualizing experiences; Social/Interpersonal: technologies used to support and improve the connectedness between individuals, groups, and organizations. Finally, we discuss the possible role of positive technologies for healthy living and active ageing by presenting different practical applications of this approach.

  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. Case Studies Involving Co-operation between Industry and Education in Australia's Northern Territory: The Role of the Professional Organisation

    ERIC Educational Resources Information Center

    Palmer, W. P.

    1990-01-01

    The purpose of this study is to provide case studies of co-operation between education and industry in the Northern Territory in particular; the study also provides exemplars of co-operation between education and industry in Australia and worldwide. The existence of such co-operation is not surprising as education and industry share many common…

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. PLAP-1/Asporin Positively Regulates FGF-2 Activity.

    PubMed

    Awata, T; Yamada, S; Tsushima, K; Sakashita, H; Yamaba, S; Kajikawa, T; Yamashita, M; Takedachi, M; Yanagita, M; Kitamura, M; Murakami, S

    2015-10-01

    PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor β activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.

  6. Mitral valve repair for active culture positive infective endocarditis

    PubMed Central

    Doukas, G; Oc, M; Alexiou, C; Sosnowski, A W; Samani, N J; Spyt, T J

    2006-01-01

    Objective To describe the clinical and echocardiographic outcome after mitral valve (MV) repair for active culture positive infective MV endocarditis. Patients and methods Between 1996 and 2004, 36 patients (mean (SD) age 53 (18) years) with positive blood culture up to three weeks before surgery (or positive culture of material removed at operation) and intraoperative evidence of endocarditis underwent MV repair. Staphylococci and streptococci were the most common pathogens. All patients had moderate or severe mitral regurgitation (MR). Mean New York Heart Association (NYHA) class was 2.3 (1.0). Follow up was complete (mean 38 (19) months). Results Operative mortality was 2.8% (one patient). At follow up, endocarditis has not recurred. One patient developed severe recurrent MR and underwent valve replacement and one patient had moderate MR. There were two late deaths, both non‐cardiac. Kaplan‐Meier five year freedom from recurrent moderate to severe MR, freedom from repeat operation, and survival were 94 (4)%, 97 (3)%, and 93 (5)%, respectively. At the most recent review the mean NYHA class was 1.17 (0.3) (p < 0.0001). At the latest echocardiographic evaluation, left atrial diameters, left ventricular end diastolic diameter, and MV diameter were significantly reduced (p < 0.05) compared with preoperative values. Conclusions MV repair for active culture positive endocarditis is associated with low operative mortality and provides satisfactory freedom from recurrent infection, freedom from repeat operation, and survival. Hence, every effort should be made to repair infected MVs and valves should be replaced only when repair is not possible. PMID:15951395

  7. 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

  8. 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…

  9. 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)

  10. 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…

  11. The Formation and Development of Co-Operations among South African Universities

    ERIC Educational Resources Information Center

    Roebken, Heinke

    2008-01-01

    Organizational collaboration is "en vogue", especially in higher education. So far, little is known about the mechanisms that explain co-operation formation and their impact on the social structure of the research systems. By examining co-authored research papers written at South African universities between 1966 and 2006, co-operation…

  12. Jamming Transition of Point-To Traffic Through Co-Operative Mechanisms

    NASA Astrophysics Data System (ADS)

    Fang, Jun; Qin, Zheng; Chen, Xiqun; Xu, Zhaohui

    2012-11-01

    We study the jamming transition of two-dimensional point-to-point traffic through co-operative mechanisms (DCM) using computer simulation. We propose two decentralized co-operative mechanisms CM which are incorporated into the point-to-point traffic models: stepping aside (CM-SA) and choosing alternative routes (CM-CAR). Incorporating CM-SA is to prevent a type of ping-pong jumps from happening when two objects standing face-to-face want to move in opposite directions. Incorporating CM-CAR is to handle the conflict when more than one object competes for the same point in parallel update. We investigate and compare four models mainly from fundamental diagrams, jam patterns and the distribution of co-operation probability. It is found that although it decreases the average velocity a little, the CM-SA increases the critical density and the average flow. Despite increasing the average velocity, the CM-CAR decreases the average flow by creating substantially vacant areas inside jam clusters. We investigate the jam patterns of four models carefully and explain this result qualitatively. In addition, we discuss the advantage and applicability of decentralized co-operation modeling.

  13. The Economic and Social Impact of the Arctic Co-operative Movement on the Canadian Eskimo.

    ERIC Educational Resources Information Center

    Jensen, Kenneth D.

    Canada's Arctic co-operatives are designed to provide a means of encouraging Eskimos to participate directly in the economic development of the Arctic through the promotion of cooperative ownership and enterprise. They also seek to provide a method of maximizing economic returns in Arctic communities from local businesses and enterprise. Backed by…

  14. 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…

  15. 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…

  16. A mixture of "cheats" and "co-operators" can enable maximal group benefit.

    PubMed

    MaClean, R Craig; Fuentes-Hernandez, Ayari; Greig, Duncan; Hurst, Laurence D; Gudelj, Ivana

    2010-09-14

    Is a group best off if everyone co-operates? Theory often considers this to be so (e.g. the "conspiracy of doves"), this understanding underpinning social and economic policy. We observe, however, that after competition between "cheat" and "co-operator" strains of yeast, population fitness is maximized under co-existence. To address whether this might just be a peculiarity of our experimental system or a result with broader applicability, we assemble, benchmark, dissect, and test a systems model. This reveals the conditions necessary to recover the unexpected result. These are 3-fold: (a) that resources are used inefficiently when they are abundant, (b) that the amount of co-operation needed cannot be accurately assessed, and (c) the population is structured, such that co-operators receive more of the resource than the cheats. Relaxing any of the assumptions can lead to population fitness being maximized when cheats are absent, which we experimentally demonstrate. These three conditions will often be relevant, and hence in order to understand the trajectory of social interactions, understanding the dynamics of the efficiency of resource utilization and accuracy of information will be necessary.

  17. Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

    PubMed Central

    Aoki, Yutaka; Helzlsouer, Kathy J.; Strickland, Paul T.

    2014-01-01

    Context: Cholinesterase (ChE) specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking) with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose. PMID:24473115

  18. 'The positive feel': Unpacking the role of positive thinking in people with multiple sclerosis's thinking aloud about staying physically active.

    PubMed

    Hall-McMaster, Samuel M; Treharne, Gareth J; Smith, Catherine M

    2016-12-01

    People with multiple sclerosis experience barriers to physical activity. Thought processes are interwoven with garnering motivation to overcome these barriers. This study investigated in-depth the role of positive thinking in physical activity motivation of two women and two men with multiple sclerosis. Participants thought aloud while completing standardised measures of physical activity, stages of change and self-efficacy, and in response to planned and spontaneous questions. Four themes were formulated using inductive thematic analysis: thoughts about purpose, self-efficacy, the past and reinforcement through positive thinking. These findings have implications for physical activity theories and delivering appropriate physical activity interventions to the multiple sclerosis community.

  19. [Introduction of a school-based intervention method targeted for drug using students. Barriers related to the co-operation between parents and teachers].

    PubMed

    Okulicz-Kozaryn, Katarzyna; Borucka, Anna; Pisarska, Agnieszka

    2003-01-01

    The aim of the study was to analyse the process of implementing a school-based intervention method, for drug using students and barriers, related to the parent-school co-operation, impeding this process. Data were collected during the qualitative evaluation of the intervention implementation into 11 schools representing various educational levels and local communities. Results indicate that in 6 schools at least some of proposed system modifications were implemented and in 7 schools teachers used key elements of the intervention method while solving problems related to students' conduct or drug use. The teachers' attitude and expectations related to the idea of family-school co-operation were important from the very beginning of the programme implementation - at the stage of establishing a sense of urgency of the change. In proceeding stages, good communication and openness in parent-school contacts were crucial for the programme effectiveness. These were also a source of positive reinforcement for the people involved.

  20. Co-operative signalling mechanisms required for erythroid precursor expansion in response to erythropoietin and stem cell factor.

    PubMed

    Arcasoy, Murat O; Jiang, Xiaohong

    2005-07-01

    The regeneration of circulating red blood cells in response to anaemia associated with blood loss or haemolysis involves an increased rate of erythropoiesis and expansion of proerythroblasts, the bone marrow precursor cells that terminally differentiate into mature erythrocytes. This study investigated the mechanisms by which erythropoietin (Epo) and stem cell factor (Scf) modulate the expansion of proerythroblasts. Homogenous populations of primary human proerythroblasts were generated in liquid cultures of CD34(+) cells. In serum-free cultures, proerythroblasts failed to survive in the presence of Epo or Scf alone, but exhibited synergistic proliferation in response to combined Epo and Scf treatment, exhibiting one-log expansion in 5 d. Intracellular signal transduction in response to Epo and Scf revealed that tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 5, a downstream target for the non-receptor tyrosine kinase, Janus kinase 2 (Jak2), was mediated by Epo but not Scf. The mitogen-activated protein kinases (MAPKs) extracellular regulated kinase (Erk) 1-2 were phosphorylated in response to either Epo or Scf. Phosphorylation of Akt, a signalling molecule downstream of phosphatidylinositol 3-kinase (PI3K), was observed following Scf but not Epo treatment. To determine the contribution of specific signalling pathways to synergistic expansion of proerythroblasts in response to co-operative effects of Epo and Scf, cells were treated with kinase inhibitors targeting Jak2, PI3K and MAPK kinase. There was a significant, dose-dependent inhibition of proerythroblast expansion in response to all three kinase inhibitors. In conclusion, Epo- and Scf-mediated co-operative, synergistic expansion of primary erythroid precursors requires selective activation of multiple signalling pathways, including the Jak-Stat, PI3K and MAPK pathways.

  1. Design and implementation of co-operative control strategy for hybrid AC/DC microgrids

    NASA Astrophysics Data System (ADS)

    Mahmud, Rasel

    This thesis is mainly divided in two major sections: 1) Modeling and control of AC microgrid, DC microgrid, Hybrid AC/DC microgrid using distributed co-operative control, and 2) Development of a four bus laboratory prototype of an AC microgrid system. At first, a distributed cooperative control (DCC) for a DC microgrid considering the state-of-charge (SoC) of the batteries in a typical plug-in-electric-vehicle (PEV) is developed. In DC microgrids, this methodology is developed to assist the load sharing amongst the distributed generation units (DGs), according to their ratings with improved voltage regulation. Subsequently, a DCC based control algorithm for AC microgrid is also investigated to improve the performance of AC microgrid in terms of power sharing among the DGs, voltage regulation and frequency deviation. The results validate the advantages of the proposed methodology as compared to traditional droop control of AC microgrid. The DCC-based control methodology for AC microgrid and DC microgrid are further expanded to develop a DCC-based power management algorithm for hybrid AC/DC microgrid. The developed algorithm for hybrid microgrid controls the power flow through the interfacing converter (IC) between the AC and DC microgrids. This will facilitate the power sharing between the DGs according to their power ratings. Moreover, it enables the fixed scheduled power delivery at different operating conditions, while maintaining good voltage regulation and improved frequency profile. The second section provides a detailed explanation and step-by-step design and development of an AC/DC microgrid testbed. Controllers for the three-phase inverters are designed and tested on different generation units along with their corresponding inductor-capacitor-inductor (LCL) filters to eliminate the switching frequency harmonics. Electric power distribution line models are developed to form the microgrid network topology. Voltage and current sensors are placed in the proper

  2. Position paper - peer review and design verification of selected activities

    SciTech Connect

    Stine, M.D.

    1994-09-01

    Position Paper to develop and document a position on the performance of independent peer reviews on selected design and analysis components of the Title I (preliminary) and Title II (detailed) design phases of the Multi-Function Waste Tank Facility project.

  3. Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII.

    PubMed

    Wagschal, Alexandre; Rousset, Emilie; Basavarajaiah, Poornima; Contreras, Xavier; Harwig, Alex; Laurent-Chabalier, Sabine; Nakamura, Mirai; Chen, Xin; Zhang, Ke; Meziane, Oussama; Boyer, Frédéric; Parrinello, Hugues; Berkhout, Ben; Terzian, Christophe; Benkirane, Monsef; Kiernan, Rosemary

    2012-09-14

    Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3'-5' exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation.

  4. 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).

  5. Power corrupts co-operation: cognitive and motivational effects in a double EEG paradigm.

    PubMed

    Kanso, Riam; Hewstone, Miles; Hawkins, Erin; Waszczuk, Monika; Nobre, Anna Christina

    2014-02-01

    This study investigated the effect of interpersonal power on co-operative performance. We used a paired electro-encephalogram paradigm: pairs of participants performed an attention task, followed by feedback indicating monetary loss or gain on every trial. Participants were randomly allocated to the power-holder, subordinate or neutral group by creating different levels of control over how a joint monetary reward would be allocated. We found that power was associated with reduced behavioural accuracy. Event-related potential analysis showed that power-holders devoted less motivational resources to their targets than did subordinates or neutrals, but did not differ at the level of early conflict detection. Their feedback potential results showed a greater expectation of rewards but reduced subjective magnitude attributed to losses. Subordinates, on the other hand, were asymmetrically sensitive to power-holders' targets. They expected fewer rewards, but attributed greater significance to losses. Our study shows that power corrupts balanced co-operation with subordinates.

  6. 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…

  7. 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…

  8. 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

  9. Inorganic lead and calcium interact positively in activation of calmodulin.

    PubMed

    Kern, M; Wisniewski, M; Cabell, L; Audesirk, G

    2000-06-01

    Calmodulin is a ubiquitous calcium-binding protein that mediates many of the intracellular actions of Ca2+ ions. The calcium-binding sites of calmodulin consist of four EF-hand motifs; full activation of calmodulin normally occurs when all four sites are occupied by Ca2+. Inorganic lead (PY2+) has been shown to activate calmodulin at total lead concentrations similar to the concentrations of Ca2+ required for activation (Goldstein and Ar, 1983; Habermann et al., 1983), but the free Pb2+ concentrations required for calmodulin activation have not been determined. In addition, it is possible that activation may occur with different sites occupied by different divalent cations, for example Ca2+ and Pb2+. We investigated the ability of free Pb2+, alone or in combination with Ca2+, to activate calmodulin. In aqueous media, N-phenyl-1-naphthylamine (NPN) and 8-anilino-1-naphthalenesulfonate (ANS) show increased fluorescence when bound to hydrophobic regions of proteins. This increased fluorescence has been used to monitor the conformational change that occurs during calmodulin activation (LaPorte et al., 1980). In the presence of calmodulin, both Ca2+ and Pb2+ stimulated increased fluorescence of NPN and ANS. Threshold and EC50 free metal concentrations were approximately 100 nM and 450-500 nM, respectively, for Ca2+ and 100 pM and 400-550 pM, respectively, for Pb2+. Fluorescence was enhanced by combinations of low concentrations of free Ca2+ and Pb2+; for example, as little as 20 pM free Pb2+ enhanced fluorescence in combination with 200 nM free Ca2+. The activity of the PDE1 isoform of cyclic nucleotide phosphodiesterase is stimulated by Ca2+/calmodulin (Wang et al., 1990). In the presence of calmodulin, we found that Ca2+ and Pb2+ activated calmodulin-stimulated PDE activity, with threshold and EC50 free metal concentrations of approximately 200 nM and 1200 nM, respectively, for Ca2+ and 300 pM and 430 pM, respectively, for Pb2+. PDE activity was stimulated by

  10. 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.

  11. Positive and negative reinforcement activate human auditory cortex.

    PubMed

    Weis, Tina; Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

    2013-01-01

    Prior studies suggest that reward modulates neural activity in sensory cortices, but less is known about punishment. We used functional magnetic resonance imaging and an auditory discrimination task, where participants had to judge the duration of frequency modulated tones. In one session correct performance resulted in financial gains at the end of the trial, in a second session incorrect performance resulted in financial loss. Incorrect performance in the rewarded as well as correct performance in the punishment condition resulted in a neutral outcome. The size of gains and losses was either low or high (10 or 50 Euro cent) depending on the direction of frequency modulation. We analyzed neural activity at the end of the trial, during reinforcement, and found increased neural activity in auditory cortex when gaining a financial reward as compared to gaining no reward and when avoiding financial loss as compared to receiving a financial loss. This was independent on the size of gains and losses. A similar pattern of neural activity for both gaining a reward and avoiding a loss was also seen in right middle temporal gyrus, bilateral insula and pre-supplemental motor area, here however neural activity was lower after correct responses compared to incorrect responses. To summarize, this study shows that the activation of sensory cortices, as previously shown for gaining a reward is also seen during avoiding a loss.

  12. Implementing agreement on a co-operative program on inertial fusion energy

    SciTech Connect

    Latkowski, J; Hogan, W; Meier, W

    2000-01-04

    The Programme to be carried out by the Contracting Parties within the framework of this Agreement shall consist of co-operative research, development, demonstrations and exchanges of information regarding inertial fusion energy (IFE). This shall include: (1) Nuclear Technology, (2) Fusion Materials, (3) Environment, Safety and Economics, (4) Laser Drivers, (5) Ion Beam Drivers and Beam/Plasma Interactions, (6) Target Production, Injection and Tracking, (7) Fusion Diagnostics, (8) Driver/Plasma Interactions, (9) Fast Ignition and (10) Power Plant Design Studies. Annexes to this agreement will describe specific tasks in each area.

  13. 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.

  14. Development of co-operative Pan-European TMN systems: EURESCOM experiences

    NASA Astrophysics Data System (ADS)

    Covaci, Stefan; Mayordomo, Eduado; Zhang, Tianning

    1996-12-01

    During the last years EURESCOM has launched a set of projects in the area of TMN addressing the problems of pan- European broadband networks and services management. The X interfaces, which provide the means for co-operative management of different domains, are the emphasis in this context. Two such X interfaces are developed for the pan- European broadband SDH/ATM services: the Xcoop interfaces situated between two public management domains and the Xuser interface which is situated between a private and a public management domain. The Xcoop interfaces support the co- operations between the Public Network Operators in providing the global connectivities, whereas the Xuser offers a means of provisioning the connectivity to the customers by enabling the customer management entities in the private domains to subscribe for the service, to access and to manage the global connectivities or related resources. This paper presents the results of the EURESCOM project P408 in specifying, implementing and testing these X interfaces, and discusses the experiences obtained.

  15. Receptor co-operation in retrovirus entry: recruitment of an auxiliary entry mechanism after retargeted binding.

    PubMed Central

    Valsesia-Wittmann, S; Morling, F J; Hatziioannou, T; Russell, S J; Cosset, F L

    1997-01-01

    We have constructed Moloney murine leukemia virus (MoMLV)-derived envelope glycoproteins (AMO) displaying an amino-terminal Ram-1-binding domain in which a variety of different amino acid spacers have been inserted between the displayed domain and the MoMLV surface (SU) subunit. Titres of retroviruses generated with these chimeric envelopes were enhanced on cells expressing both Ram-1 and Rec-1 receptors compared with the titres on cells expressing only one or other receptor type. The absolute viral titres and the degree of titre enhancement due to receptor cooperativity were highly variable between the different chimeric envelopes and were determined primarily by the properties of the interdomain spacer. An extreme example of receptor co-operativity was encountered when testing Ram-1-targeted AMOPRO envelopes with specific proline-rich interdomain spacers. AMOPRO viruses could not enter cells expressing only Rec-1 or only Ram-1 but could efficiently infect cells co-expressing both receptors. The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec-1) receptor which leads to optimal fusion triggering. PMID:9135138

  16. Power corrupts co-operation: cognitive and motivational effects in a double EEG paradigm

    PubMed Central

    Kanso, Riam; Hewstone, Miles; Hawkins, Erin; Waszczuk, Monika; Nobre, Anna Christina

    2014-01-01

    This study investigated the effect of interpersonal power on co-operative performance. We used a paired electro-encephalogram paradigm: pairs of participants performed an attention task, followed by feedback indicating monetary loss or gain on every trial. Participants were randomly allocated to the power-holder, subordinate or neutral group by creating different levels of control over how a joint monetary reward would be allocated. We found that power was associated with reduced behavioural accuracy. Event-related potential analysis showed that power-holders devoted less motivational resources to their targets than did subordinates or neutrals, but did not differ at the level of early conflict detection. Their feedback potential results showed a greater expectation of rewards but reduced subjective magnitude attributed to losses. Subordinates, on the other hand, were asymmetrically sensitive to power-holders’ targets. They expected fewer rewards, but attributed greater significance to losses. Our study shows that power corrupts balanced co-operation with subordinates. PMID:23160813

  17. Situational trust and co-operative partnerships between physicians and their patients: a theoretical explanation transferable from business practice.

    PubMed

    Dibben, M R; Morris, S E; Lean, M E

    2000-01-01

    A model to explain interpersonal trust development, and its consequences for co-operative behaviour in doctor/patient partnerships derived from the context of business relationships is applied to patient/physician relationships. Threshold barriers exist against all human behaviours or actions and trust is the process by which barriers to co-operation and compliance are overcome. Dispositional trust (a psychological trait to be trusting) is dominant in the early stages of a relationship and contributes to the weight of subsequent trust development. Co-operative behaviour or compliance ultimately requires a secure situational trust emerging from consultations, which is carried forward as learnt trust and modified in each subsequent consultation. The model comprises three types of situational trust (calculus-based, knowledge-based, and identification trust) and five co-operation criteria from which to determine an individual's tendency for co- operative behaviour. These model components can be identified and mapped from a range of qualitative data, with the aim of enhancing co-operative behaviour and efficiently achieving optimal patient compliance.

  18. Facets of dynamic positive affect: differentiating joy, interest, and activation in the positive and negative affect schedule (PANAS).

    PubMed

    Egloff, Boris; Schmukle, Stefan C; Burns, Lawrence R; Kohlmann, Carl-Walter; Hock, Michael

    2003-09-01

    This article proposes the differentiation of Joy, Interest, and Activation in the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS; D. Watson, L. A. Clark, & A. Tellegen, 1988). Study 1 analyzed the dynamic course of PA before, during, and after an exam and established the differentiation of the three facets. Study 2 used a multistate-multitrait analysis to confirm this structure. Studies 3-5 used success-failure experiences, speaking tasks, and feedback of exam results to further examine PA facets in affect-arousing settings. All studies provide convincing evidence for the benefit of differentiating three facets of PA in the PANAS: Joy, Interest, and Activation do have distinct and sometimes even opposite courses that make their separation meaningful and rewarding.

  19. 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…

  20. Challenge and co-operation: civil society activism for access to HIV treatment in Thailand.

    PubMed

    Ford, Nathan; Wilson, David; Cawthorne, Paul; Kumphitak, Aree; Kasi-Sedapan, Siriras; Kaetkaew, Suntharaporn; Teemanka, Saengsri; Donmon, Boripat; Preuanbuapan, Chalerm

    2009-03-01

    Civil society has been a driving force behind efforts to increase access to treatment in Thailand. A focus on HIV medicines brought civil society and non-governmental and government actors together to fight for a single cause, creating a platform for joint action on practical issues to improve care for people with HIV/AIDS (PHA) within the public health system. The Thai Network of People with HIV/AIDS, in partnership with other actors, has provided concrete support for patients and for the health system as a whole; its efforts have contributed significantly to the availability of affordable generic medicines, early treatment for opportunistic infections, and an informed and responsible approach towards antiretroviral treatment that is critical to good adherence and treatment success. This change in perception of PHA from 'passive receiver' to 'co-provider' of health care has led to improved acceptance and support within the healthcare system. Today, most PHA in Thailand can access treatment, and efforts have shifted to supporting care for excluded populations.

  1. Caffeinated coffee enhances co-operative behavior in the Mixed Motive Game in healthy volunteers.

    PubMed

    Tse, Wai S; Chan, Chi Choi S; Shiu, Shun Yan K; Chung, Pik Yee A; Cheng, Shuk Han

    2009-02-01

    Caffeinated drinks are commonly consumed in social gatherings. However, their effects on social behavior remain unclear. The present study examined the effects of caffeinated coffee on antidepressant-related co-operative behavior. Seventy-seven low-caffeine users took part in a randomized, double-blind, cross-over study of single dose of caffeinated coffee (150 mg caffeine) and decaffeinated coffee (9 mg caffeine) with at least a 3-day washout period. In each session, participants were asked to imagine a fictitious person and play the Mixed Motive Game with that person 45 min after coffee consumption. Heart rate, blood pressure, and state moods were measured at baseline and at 45 min post-coffee consumption. After caffeinated coffee, participants exhibited significantly higher blood pressure. They also allocated significantly fewer scores to themselves and sent significantly more sadness message during the game. These results suggest that caffeinated coffee may help to improve social support and depressive symptoms.

  2. 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

  3. Co-operation with eastern European countries taking ENAC as an example

    SciTech Connect

    Taylor, D.

    1994-12-31

    In the aftermath of the Chernobyl accident, the European Community launched an ambitious programme of nuclear safety assistance. The purpose of this programme is to improve the safety of the Nuclear Power stations in Eastern Europe and the former Soviet Union plants. It was felt in the Western European nuclear industry that the emphasis should be on finding practical solutions to improve the most urgent problems. To achieve this objective, the nuclear industry in Western Europe founded a consortium called ENAC (European Nuclear Assistance Consortium) comprising companies form seven European countries (Great Britain, France, Germany, Spain, Belgium, Italy, Netherlands). The co-operation between these companies and the Russian designers would ensure that the solutions developed meet the approval of all interested parties.

  4. Co-operative action of calcium ions in dopamine release from rat brain synaptosomes.

    PubMed Central

    Nachshen, D A; Sanchez-Armass, S

    1987-01-01

    1. The release of [3H]dopamine from isolated presynaptic nerve terminals (synaptosomes) prepared from rat striata was measured as a function of the external Ca2+ concentration ([Ca2+]o). 2. In synaptosomes depolarized by the addition of 50 mM-K+, release of [3H]dopamine increased in a highly non-linear manner with [Ca2+]o. The release could be described as a third power function of [Ca2+]o. 3. Both 45Ca2+ influx and the change in the free cytosolic Ca2+ concentration ([Ca2+]i, measured with the fluorescent Ca2+ indicator fura-2) that were evoked by depolarization increased in a linear manner with [Ca2+]o. 4. These results suggest that non-linearity in the [Ca2+]o dependence of transmitter release originates in a co-operative relation between [Ca2+]i and exocytosis. PMID:3656180

  5. WHO Co-operative studies on a simple culture technique for the isolation of mycobacteria

    PubMed Central

    Šula, Ladislav

    1963-01-01

    Tuberculosis surveys are in progress in many countries that do not have adequate laboratory facilities for carrying out complicated bacteriological procedures. As part of a WHO co-operative research programme, studies have been undertaken with a view to developing a simple culture technique for the isolation of mycobacteria that does not require elaborate equipment. This paper is the first report on these co-operative studies. Storage and transport are known to affect adversely the viability of Mycobacterium tuberculosis in pathological specimens, thus giving rise to poor culture results and indicating the advisability of culturing such specimens on the spot. The preparation of the efficient and widely used Löwenstein-Jensen (L-J) culture medium, however, requires materials and facilities that are not easy available in developing countries. In an attempt to overcome this difficulty, the Tuberculosis Research Institute in Prague has developed a semi-synthetic liquid medium that can be prepared in bulk, concentrated and lyophilized, and sent even to distant laboratories. The present paper describes in detail the preparation of this lyophilized medium, which can be stored at room temperature for at least 6-12 months and is easy to reconstitute, and discusses the growth characteristics of mycobacteria multiplied in it. Experience in Czechoslovakia, where between 1953 and 1962 nearly 21 million cultures have been made with the medium, has shown that it is quite satisfactory and even slightly superior to L-J medium in certain respects. ImagesFIG. 1FIG. 2FIG. 3 & 4FIG. 9FIG. 10FIG. 11FIG. 12FIG. 5FIG. 6FIG. 7FIG. 8FIG. 13FIG. 14FIG. 15FIG. 16 PMID:14102036

  6. Empathy is associated with dynamic change in prefrontal brain electrical activity during positive emotion in children

    PubMed Central

    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 infants and children is well known. The relationship between positive emotion (assessed via parent-report), empathy (measured via observation) and second-by-second brain electrical activity (recorded during a pleasurable task) was investigated using a sample of 128 six to ten year olds. Contentment predicted increasing left-sided frontopolar activation (p<.05). Empathic concern and one form of positive empathy predicted increasing right-sided frontopolar activation (ps<.05). A second form of positive empathy predicted increasing left-sided dorsolateral activation (p<.05). This suggests that positive emotion and (negative and positive) empathy predict changes in prefrontal activity in children during a pleasurable task. PMID:19630903

  7. A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc− Mediates Aglycemic Neuronal Cell Death

    PubMed Central

    Thorn, Trista L.; He, Yan; Jackman, Nicole A.; Lobner, Doug; Hewett, James A.

    2015-01-01

    The astrocyte cystine/glutamate antiporter (system xc−) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc− expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc− mediates aglycemic neuronal cell death. PMID:26553727

  8. 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.

  9. Wound care in primary health care: district nurses' needs for co-operation and well-functioning organization.

    PubMed

    Friman, Anne; Klang, Birgitta; Ebbeskog, Britt

    2010-01-01

    Most patients with leg- and foot ulcers are managed within non-institutional care. The aim of this study was to investigate the district nurses' wound management, including wound appearance, assignment of responsibility, guidelines for wound treatment and co-operation with other professional groups. The study has a descriptive quantitative approach. Data was collected using a wound registration form and a questionnaire. The selection of participants was made by random sampling. District nurses (n = 26) in five health-care centers situated in central Stockholm and two of its suburbs, participated in the study. The results show that the wound appearance is dominated by traumatic wounds. Approximately 40% of the wounds were not medically diagnosed. The area of responsibility of different professional groups was not defined and guidelines for wound treatment were mostly lacking. The decision about wound management was generally made by the district nurse. Co-operation with the general practitioner was lacking and when a consultation with dermatologist was required, the routines concerning referral were undefined. Co-operation with the assistant nurses consisted of redressing the wounds in home care. Interprofessional co-operation was regarded as important for wound healing. The paper provides insights into the district nurses' wound management and co-operation in wound care.

  10. The position of prenylation of isoflavonoids and stilbenoids from legumes (Fabaceae) modulates the antimicrobial activity against Gram positive pathogens.

    PubMed

    Araya-Cloutier, Carla; den Besten, Heidy M W; Aisyah, Siti; Gruppen, Harry; Vincken, Jean-Paul

    2017-07-01

    The legume plant family (Fabaceae) is a potential source of antimicrobial phytochemicals. Molecular diversity in phytochemicals of legume extracts was enhanced by germination and fungal elicitation of seven legume species, as established by RP-UHPLC-UV-MS. The relationship between phytochemical composition, including different types of skeletons and substitutions, and antibacterial properties of extracts was investigated. Extracts rich in prenylated isoflavonoids and stilbenoids showed potent antibacterial activity against Listeria monocytogenes and methicillin-resistant Staphylococcus aureus at concentrations between 0.05 and 0.1% (w/v). Prenylated phenolic compounds were significantly (p<0.01) correlated with the antibacterial properties of the extracts. Furthermore, the position of the prenyl group within the phenolic skeleton also influenced the antibacterial activity. Overall, prenylated phenolics from legume seedlings can serve multiple purposes, e.g. as phytoestrogens they can provide health benefits and as natural antimicrobials they offer preservation of foods.

  11. Influence of pelvis position on the activation of abdominal and hip flexor muscles.

    PubMed

    Workman, J Chad; Docherty, David; Parfrey, Kevin C; Behm, David G

    2008-09-01

    A pelvic position has been sought that optimizes abdominal muscle activation while diminishing hip flexor activation. Thus, the objective of the study was to investigate the effect of pelvic position and the Janda sit-up on trunk muscle activation. Sixteen male volunteers underwent electromyographic (EMG) testing of their abdominal and hip flexor muscles during a supine isometric double straight leg lift (DSLL) with the feet held approximately 5 cm above a board. The second exercise (Janda sit-up) was a sit-up action where participants simultaneously contracted the hamstrings and the abdominal musculature while holding an approximately 45 degrees angle at the knee. Root mean square surface electromyography was calculated for the Janda sit-up and DSLL under 3 pelvic positions: anterior, neutral, and posterior pelvic tilt. The selected muscles were the upper and lower rectus abdominis (URA, LRA), external obliques, lower abdominal stabilizers (LAS), rectus femoris, and biceps femoris. The Janda sit-up position demonstrated the highest URA and LRA activation and the lowest rectus femoris activation. The Janda sit-up and the posterior tilt were significantly greater (p < 0.01 and p < 0.05, respectively) than the anterior tilt for the URA and LRA muscles. Activation levels of the URA and LRA in neutral pelvis were significantly (p < 0.01 and p < 0.05, respectively) less than the Janda sit-up position, but not significantly different from the posterior tilt. No significant differences in EMG activity were found for the external obliques or LAS. No rectus femoris differences were found in the 3 pelvis positions. The results of this study indicate that pelvic position had a significant effect on the activation of selected trunk and hip muscles during isometric exercise, and the activation of the biceps femoris during the Janda sit-up reduced the activation of the rectus femoris while producing high levels of activation of the URA and LRA.

  12. Management of recycling in the Gulf Co-operation Council states.

    PubMed

    Alhumoud, Jasem M; Al-Ghusain, Ibrahim; Al-Hasawi, Hamad

    2004-01-01

    Although some of the Gulf Co-operation Council (GCC) member states have placed recycling at the top of their waste management priorities, the low cost of landfill and the availability of land, usually old sand or gravel quarries, make recycling programs infeasible, uneconomical and unachievable. The only comprehensive form of recycling available within the GCC states is recycling of paper and cartons. The majority of the GCC states never set national or regional recycling targets. The cost of recycling in the GCC states region could be moderate to high depending on the collection system selected for the recycling program. Almost all of the cities within the GCC states use mechanised systems for daily collection of municipal solid waste (MSW). Therefore, the same daily collection system used for MSW might well be used for collection of recyclable materials, both on the same day and at the same time, or according to a different timetable. This paper provides strategies for developing an effective recycling marketing program and discusses regional co-ordination options.

  13. Concentrating on Solar Power in a Trans-Mediterranean Renewable Energy Co-Operation

    NASA Astrophysics Data System (ADS)

    Trieb, F.; Kronshage, S.; Knies, G.

    2004-12-01

    Combining the large demand of clean electricity in Europe (EU) with the large potential of solar electricity generation from concentrating solar power stations (CSP) in the Middle East and North Africa (MENA) can provide both climate protection and development for both regions and lead to environmental, economical and social sustainability. The presentation will address the concept of solar cogeneration of electricity and desalted water and the scope of generating clean power for MENA and Europe while providing large quantities of freshwater for the MENA countries. Costs and benefits of the concept will be quantified, and the first steps to realisation within the Trans-Mediterranean Renewable Energy Co-Operation TREC are presented. After running through the technology learning curve within about 10-15 years, concentrated solar electricity will be generated at a cost of roughly 4 ct/kWh. Importing solar power from North Africa to Europe, will add 1 ct/kWh, thus being competitive with new fuel fired plants. The total initial support of about 1 billion € needed to trigger CSP market introduction and to achieve forever low electricity costs in the EU and MENA, equals 25 % of the German annual coal subsidies, 1 month of EU agronomic-subsidies or 1 day of US military expenses and could be provided in form of public investment, soft loans or feed-in guaranties like the German Renewable Energy Act.

  14. LXR activation inhibits chemokine-induced CD4-positive lymphocyte migration.

    PubMed

    Walcher, Daniel; Vasic, Dusica; Heinz, Philipp; Bach, Helga; Durst, Renate; Hausauer, Angelina; Hombach, Vinzenz; Marx, Nikolaus

    2010-07-01

    Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that CD4-positive lymphocytes express the nuclear transcription factors Liver-X-Receptor (LXR) alpha and beta with an effect of LXR activators on TH1-cytokine release from these cells. However, the role of LXR in lymphocyte migration remains currently unexplored. Therefore, the present study investigated whether LXR activation might modulate chemokine-induced migration of these cells. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.5 +/- 0.8-fold increase in cell migration (P < 0.05; n = 12). Pretreatment of cells with the LXR activator T0901317 reduces this effect in a concentration-dependent manner to a maximal 0.9 +/- 0.4-fold induction at 1 micromol/L T0901317 (P < 0.05 compared to SDF-1-treated cells; n = 12). Similar results were obtained with the LXR activator GW3965. The effect of LXR activators on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, T0901317 inhibited activation of the small GTPase Rac and phosphorylation of the myosin light chain (MLC). Moreover, LXR activator treatment reduced f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Transfection of CD4-positive lymphocytes with LXRalpha/beta siRNA abolished T0901317 inhibitory effect on MLC phosphorylation and ICAM3 translocation. LXR activation by T0901317 or GW3965 inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T cell migration in early atherogenesis, LXR activators may be promising tools to modulate this effect.

  15. Positivity effect in healthy aging in observational but not active feedback-learning.

    PubMed

    Bellebaum, Christian; Rustemeier, Martina; Daum, Irene

    2012-01-01

    The present study investigated the impact of healthy aging on the bias to learn from positive or negative performance feedback in observational and active feedback learning. In active learning, a previous study had already shown a negative learning bias in healthy seniors older than 75 years, while no bias was found for younger seniors. However, healthy aging is accompanied by a 'positivity effect', a tendency to primarily attend to stimuli with positive valence. Based on recent findings of dissociable neural mechanisms in active and observational feedback learning, the positivity effect was hypothesized to influence older participants' observational feedback learning in particular. In two separate experiments, groups of young (mean age 27) and older participants (mean age 60 years) completed an observational or active learning task designed to differentially assess positive and negative learning. Older but not younger observational learners showed a significant bias to learn better from positive than negative feedback. In accordance with previous findings, no bias was found for active learning. This pattern of results is discussed in terms of differences in the neural underpinnings of active and observational learning from performance feedback.

  16. Effect of Knee Position on Quadriceps Muscle Force Steadiness and Activation Strategies

    PubMed Central

    Krishnan, Chandramouli; Allen, Eric J.; Williams, Glenn N.

    2010-01-01

    Introduction This study investigated the effect of knee position on quadriceps force steadiness and activation strategies. Methods Quadriceps force steadiness was evaluated in twenty-two volunteers at two knee positions by testing their ability to regulate submaximal force. Muscle activation strategies were studied in both time and frequency domains using surface electromyography. Results Quadriceps force fluctuations and the associated agonist and antagonist activity were significantly higher at 90° than at 30° of flexion (P < 0.05). The quadriceps median frequency recorded at 30° was significantly higher than at 90° of flexion (P < 0.05). Regression analyses revealed that force steadiness was related to quadriceps activation and median frequency (P < 0.001), but not to hamstring coactivation (P > 0.05). Discussion The results indicate that knee position significantly affects quadriceps force steadiness and activation strategies. This finding may have important implications for designing a force control testing protocol and interpreting test results. PMID:21404288

  17. Activity of the positive and negative reinforcement motivation systems and baseline arterial blood pressure in humans.

    PubMed

    Aftanas, L I; Sidorova, P V; Pavlov, S V; Makhnev, V P; Korenek, V V; Reva, N V; Amstislavskaya, T G

    2008-10-01

    The aim of the present work was to identify possible associations between individual balances in the activity of the positive and negative reinforcement motivation systems using a method based on emotional modulation of the startle reaction (EMSR) by motivationally significant emotionally positive and negative contextual visual stimuli and measures of cardiovascular system activity. Studies were performed using healthy males (mean age 30.29 +/- 9.8 years) with normal and first-episode excessive increases in arterial blood pressure (systolic blood pressure to greater than 140 mmHg, diastolic to greater than 90 mmHg). Cluster analysis of EMSR data identified groups of individuals with different activity profiles for the positive and negative reinforcement systems. Groups of subjects with changes in the balance of activity towards a lower level of positive reinforcement system activity (smaller startle reflexes to positive contextual stimuli) or a higher level of negative reinforcement system activity (larger startle reactions to threatening contextual stimuli) showed significantly greater baseline SBP and DBP. The possible mechanisms of the modulatory influences of the balance of system activities on autonomic vascular regulatory processes are discussed.

  18. 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…

  19. 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…

  20. The Organisation for Economic Co-Operation and Development's International Early Learning Study: Opening for Debate and Contestation

    ERIC Educational Resources Information Center

    Moss, Peter; Dahlberg, Gunilla; Grieshaber, Susan; Mantovani, Susanna; May, Helen; Pence, Alan; Rayna, Sylvie; Swadener, Beth Blue; Vandenbroeck, Michel

    2016-01-01

    The Organisation for Economic Co-operation and Development is initiating the International Early Learning Study, a cross-national assessment of early learning outcomes involving the testing of 5-year-old children in participating countries. The authors use this colloquium to inform members of the early childhood community about this project and to…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. Situational Motivation and Perceived Intensity: Their Interaction in Predicting Changes in Positive Affect from Physical Activity

    PubMed Central

    Guérin, Eva; Fortier, Michelle S.

    2012-01-01

    There is evidence that affective experiences surrounding physical activity can contribute to the proper self-regulation of an active lifestyle. Motivation toward physical activity, as portrayed by self-determination theory, has been linked to positive affect, as has the intensity of physical activity, especially of a preferred nature. The purpose of this experimental study was to examine the interaction between situational motivation and intensity [i.e., ratings of perceived exertion (RPE)] in predicting changes in positive affect following an acute bout of preferred physical activity, namely, running. Fourty-one female runners engaged in a 30-minute self-paced treadmill run in a laboratory context. Situational motivation for running, pre- and post-running positive affect, and RPE were assessed via validated self-report questionnaires. Hierarchical regression analyses revealed a significant interaction effect between RPE and introjection (P < .05) but not between RPE and identified regulation or intrinsic motivation. At low levels of introjection, the influence of RPE on the change in positive affect was considerable, with higher RPE ratings being associated with greater increases in positive affect. The implications of the findings in light of SDT principles as well as the potential contingencies between the regulations and RPE in predicting positive affect among women are discussed. PMID:22778914

  6. Breadth and Intensity of Youth Activity Involvement as Contexts for Positive Development

    ERIC Educational Resources Information Center

    Rose-Krasnor, Linda; Busseri, Michael A.; Willoughby, Teena; Chalmers, Heather

    2006-01-01

    Research has linked youth activity involvement to positive development. However, past studies have confounded at least two separable dimensions of involvement: breadth (number of activities) and intensity (participation frequency). Theory and the limited available evidence suggest that these dimensions may make independent contributions to…

  7. 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…

  8. 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…

  9. 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…

  10. Is spinal excitability of the triceps surae mainly affected by muscle activity or body position?

    PubMed

    Cattagni, T; Martin, A; Scaglioni, G

    2014-06-15

    The aim of this study was to determine how muscle activity and body orientation contribute to the triceps surae spinal transmission modulation, when moving from a sitting to a standing position. Maximal Hoffmann-reflex (Hmax) and motor potential (Mmax) were evoked in the soleus (SOL), medial and lateral gastrocnemius in 10 male subjects and in three conditions, passive sitting, active sitting and upright standing, with the same SOL activity in active sitting and upright standing. Moreover volitional wave (V) was evoked in the two active conditions (i.e., active sitting and upright standing). The results showed that SOL Hmax/Mmax was lower in active sitting than in passive sitting, while for the gastrocnemii it was not significantly altered. For the three plantar flexors, Hmax/Mmax was lower in upright standing than in active sitting, whereas V/Mmax was not modulated. SOL H-reflex is therefore affected by the increase in muscle activity and change in body orientation, while, in the gastrocnemii, it was only affected by a change in posture. In conclusion, passing from a sitting to a standing position affects the Hmax/Mmax of the whole triceps surae, but the mechanisms responsible for this change differ among the synergist muscles. The V/Mmax does not change when upright stance is assumed. This means that the increased inhibitory activity in orthostatic position is compensated by an increased excitatory inflow to the α-motoneurons of central and/or peripheral origin.

  11. Elm1 kinase activates the spindle position checkpoint kinase Kin4

    PubMed Central

    Caydasi, Ayse Koca; Kurtulmus, Bahtiyar; Orrico, Maria I.L.; Hofmann, Astrid; Ibrahim, Bashar

    2010-01-01

    Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck–associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4. PMID:20855503

  12. Elm1 kinase activates the spindle position checkpoint kinase Kin4.

    PubMed

    Caydasi, Ayse Koca; Kurtulmus, Bahtiyar; Orrico, Maria I L; Hofmann, Astrid; Ibrahim, Bashar; Pereira, Gislene

    2010-09-20

    Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.

  13. Laparoscopic and endoscopic co-operative surgery for non-ampullary duodenal tumors

    PubMed Central

    Ichikawa, Daisuke; Komatsu, Shuhei; Dohi, Osamu; Naito, Yuji; Kosuga, Toshiyuki; Kamada, Kazuhiro; Okamoto, Kazuma; Itoh, Yoshito; Otsuji, Eigo

    2016-01-01

    AIM To assess the safety and feasibility of laparoscopic and endoscopic co-operative surgery (LECS) for early non-ampullary duodenal tumors. METHODS Twelve patients with a non-ampullary duodenal tumor underwent LECS at our hospital. One patient had two mucosal lesions in the duodenum. The indication for this procedure was the presence of duodenal tumors with a low risk for lymph node metastasis. In particular, the tumors included small (less than 10 mm) submucosal tumors (SMT) and epithelial mucosal tumors, such as mucosal cancers or large mucosal adenomas with malignant suspicion. The LECS procedures, such as full-thickness dissection for SMT and laparoscopic reinforcement after endoscopic submucosal dissection (ESD) for epithelial tumors, were performed for the 13 early duodenal lesions in 12 patients. Here we present the short-term outcomes and evaluate the safety and feasibility of this new technique. RESULTS Two SMT-like lesions and eleven superficial epithelial tumor-like lesions were observed. Seven and Six lesions were located in the second and third parts of the duodenum, respectively. All lesions were successfully resected en bloc. The defect in the duodenal wall was manually sutured after resection of the duodenal SMT. For epithelial duodenal tumors, the ulcer bed was laparoscopically reinforced via manual suturing after ESD. Intraoperative perforation occurred in two out of eleven epithelial tumor-like lesions during ESD; however, they were successfully laparoscopically repaired. The median operative time and intraoperative estimated blood loss were 322 min and 0 mL, respectively. Histological examination of the tumors revealed one adenoma with moderate atypia, ten adenocarcinomas, and two neuroendocrine tumors. No severe postoperative complications (Clavien-Dindo classification grade III or higher) were reported in this series, but minor leakage secondary to pancreatic fistula occurred in one patient. CONCLUSION LECS can be a safe and minimally

  14. 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.

  15. 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.

  16. Electromyographic activity of preterm newborns in the kangaroo position: a cohort study

    PubMed Central

    Miranda, Rafael Moura; Cabral Filho, José Eulálio; Diniz, Kaísa Trovão; Souza Lima, Geisy Maria; Vasconcelos, Danilo de Almeida

    2014-01-01

    Objective To compare the electromyographic activity of preterm newborns placed in the kangaroo position with the activity of newborns not placed in this position. Design A cohort study. Setting A Kangaroo Unit sector and a Nursery sector in a secondary and tertiary care at a mother-child hospital in Recife, Brazil. Participants Preterm infants of gestational age 27–34 weeks (n=38) and term infants (n=39). Primary and secondary outcome measures Surface electromyography was used to investigate muscle activity in the brachial biceps at rest. 3 groups were designed: (1) preterm newborns in the kangaroo position (PT-KAN), where the newborn remains in a vertical position, lying face down, with limbs flexed, dressed in light clothes, maintaining skin-to-skin contact with the adult's thorax. Her electromyographic activity was recorded at 0 h (immediately before starting this position), and then at 48 h after the beginning of the position (but newborns were kept in the kangaroo position for 8–12 h per day) and at term equivalent age (40±1 weeks); (2) preterm newborns not in the kangaroo position (PT-NKAN), in which measurements were made at 0 h and 48 h; and (3) term newborns (T), in which measurements were made at 24 h of chronological age. Results The Root Mean Square (RMS) values showed significant differences among groups (F(5,108)=56.69; p<0.001). The multiple comparisons showed that RMS was greater at 48 h compared to 0 h in the preterm group in the kangaroo position, but not in the group not submitted in the kangaroo position. The RMS in the term equivalent aged group in the kangaroo position was also greater when compared with those in the term group. Conclusions The kangaroo position increases electromyographic activity in the brachial biceps of preterm newborns and those who have reached the age equivalent to term. PMID:25351598

  17. American College of Sports Medicine position stand. Exercise and physical activity for older adults.

    PubMed

    Chodzko-Zajko, Wojtek J; Proctor, David N; Fiatarone Singh, Maria A; Minson, Christopher T; Nigg, Claudio R; Salem, George J; Skinner, James S

    2009-07-01

    The purpose of this Position Stand is to provide an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The Position Stand is divided into three sections: Section 1 briefly reviews the structural and functional changes that characterize normal human aging, Section 2 considers the extent to which exercise and physical activity can influence the aging process, and Section 3 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on health and functional capacity. Although no amount of physical activity can stop the biological aging process, there is evidence that regular exercise can minimize the physiological effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults. Ideally, exercise prescription for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. The evidence reviewed in this Position Stand is generally consistent with prior American College of Sports Medicine statements on the types and amounts of physical activity recommended for older adults as well as the recently published 2008 Physical Activity Guidelines for Americans. All older adults should engage in regular physical activity and avoid an inactive lifestyle.

  18. Comparison of muscle activation using various hand positions during the push-up exercise.

    PubMed

    Cogley, Robert M; Archambault, Teasha A; Fibeger, Jon F; Koverman, Mandy M; Youdas, James W; Hollman, John H

    2005-08-01

    Popular fitness literature suggests that varied hand placements during push-ups may isolate different muscles. Scientific literature, however, offers scant evidence that varied hand placements elicit different muscle responses. This study examined whether different levels of electromyographic (EMG) activity in the pectoralis major and triceps brachii muscles are required to perform push-ups from each of 3 different hand positions: shoulder width base, wide base, and narrow base hand placements. Forty subjects, 11 men and 29 women, performed 1 repetition of each push-up. The EMG activity for subjects' dominant arm pectoralis major and triceps brachii was recorded using surface electrodes. The EMG activity was greater in both muscle groups during push-ups performed from the narrow base hand position compared with the wide base position (p < 0.05). This study suggests that, if a goal is to induce greater muscle activation during exercise, then push-ups should be performed with hands in a narrow base position compared with a wide base position.

  19. Role of Positional Hydrophobicity in the Leishmanicidal Activity of Magainin 2

    PubMed Central

    Guerrero, Esther; Saugar, José María; Matsuzaki, Katsumi; Rivas, Luis

    2004-01-01

    The emergence of membrane-active antimicrobial peptides as new alternatives against pathogens with multiantibiotic resistance requires the design of better analogues. Among the different physicochemical parameters involved in the optimization of linear antimicrobial peptides, positional hydrophobicity has recently been incorporated. This takes into consideration the concept of the topological distribution of hydrophobic residues throughout the sequence rather than the classical concept of hydrophobicity as a global parameter of the peptide, calculated as the summation of the individual hydrophobicities of the residues. In order to assess the contribution of this parameter to the leishmanicidal mechanisms of magainin 2 analogues, the activities of two of these analogues, MG-H1 (GIKKFLHIIWKFIKAFVGEIMNS) and MG-H2 (IIKKFLHSIWKFGKAFVGEIMNI), which have similar charges, amino acid compositions, and hydrophobicities but different positional hydrophobicities, against Leishmania donovani promastigotes were assayed (T. Tachi, R. F. Epand, R. M. Epand, and K. Matsuzaki, Biochemistry 41:10723-10731, 2002). The activities were compared with that of the parental peptide, F5W-magainin 2 (GIGKWLHSAKKFGKAFVGEIMNS). The three peptides were active at micromolar concentrations, in the order MG-H2 > MG-H1 > F5W-magainin 2. These activities differ from their hemolytic and bactericidal activities. The results demonstrate that positional hydrophobicity, which reflects the presence of short stretches of sequences rich in hydrophobic amino acids, plays an important role in the activities of leishmanicidal peptides. PMID:15273109

  20. Influence of hip position and gender on active hip internal and external rotation.

    PubMed

    Simoneau, G G; Hoenig, K J; Lepley, J E; Papanek, P E

    1998-09-01

    A general lack of descriptive details exists for measurements of hip rotation range of motion. This study was designed to establish the influence of gender and hip flexion position on active range of motion of the hip in external and internal rotation. Sixty (39 females and 21 males) healthy college-age (21.8 +/- 1.7 years) subjects were studied. Hip rotation of the dominant leg of each subject was measured in the prone (hip near 0 degree of flexion) and seated (hip near 90 degrees of flexion) positions using a standard goniometer. Data were analyzed using an analysis of variance model. Pearson's r statistics were used to determine the degree of association between measurements of hip rotation made seated vs. prone. A statistically significant difference (p < 0.05) was found between mean hip external rotation (ER) measured seated (36 +/- 7 degrees) and mean hip ER measured prone (45 +/- 10 degrees). Conversely, mean hip internal rotation (IR) measured seated (33 +/- 7 degrees) was not statistically different than mean hip IR measured prone (36 +/- 9 degrees). Females had statistically more active hip internal and external rotation than males (p < 0.05). A moderate degree of association existed between measurements of hip ER taken in the prone vs. seated position (r = 0.57, p < 0.05). For IR, the degree of association between the two measurement positions was slightly higher (r = 0.72, p < 0.05). Unlike the amount of active hip internal rotation which showed little difference between measurements made prone vs. seated, our data indicate that measurement position had a significant effect on the amount of active range of motion of the hip in ER. These findings are clinically significant for they stress the importance of documenting measurement position. They also stress the need for representative norms to be established for each hip position and gender.

  1. Cortical activity differs between position- and force-control knee extension tasks.

    PubMed

    Poortvliet, Peter C; Tucker, Kylie J; Finnigan, Simon; Scott, Dion; Sowman, Paul; Hodges, Paul W

    2015-12-01

    Neural control differs between position- and force-control tasks as evident from divergent effects of fatigue and pain. Unlike force-control tasks, position-control tasks focus on a postural goal to maintain a joint angle. Cortical involvement is suggested to be less during postural control, but whether this differs between position- and force-control paradigms remains unclear. Coherence estimates the functional communication between spatially distinct active regions within the cortex (cortico-cortical coherence; CCC) and between the cortex and muscles (corticomuscular coherence; CMC). We investigated whether cortical involvement differed between force-control and more posturally focused, position-control tasks. Seventeen adults performed position- and force-control knee extensor efforts at a submaximal load (10 % maximum voluntary contraction). Surface electromyography was recorded from the right knee extensor and flexor muscles and brain activity using electroencephalography (EEG). CCC and CMC in the beta (13-30 Hz) and gamma (30-45 Hz) frequency bands were calculated between combinations of intra- and inter-hemispheric pairs of electrodes, and between four EEG electrodes that approximated the left motor cortical area, and right knee extensor EMG, respectively. Differences in EEG power and muscle activity were also calculated. CCC was greater across distributed regions in the force-control task. Beta EEG power in the left hemisphere was higher for the position-control task. Although averaged CMC data differed between tasks, there was no task difference for individual CMC data. Muscle activity and force did not differ between tasks. The results demonstrate differential cortical contributions to control force- versus position-control tasks. This might contribute to differences in performance outcomes of these tasks that have been shown previously.

  2. 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.

  3. Active nucleosome positioning beyond intrinsic biophysics is revealed by in vitro reconstitution.

    PubMed

    Korber, Philipp

    2012-04-01

    Genome-wide nucleosome maps revealed well-positioned nucleosomes as a major theme in eukaryotic genome organization. Promoter regions often show a conserved pattern with an NDR (nucleosome-depleted region) from which regular nucleosomal arrays emanate. Three mechanistic contributions to such NDR-array-organization and nucleosome positioning in general are discussed: DNA sequence, DNA binders and DNA-templated processes. Especially, intrinsic biophysics of DNA sequence preferences for nucleosome formation was prominently suggested to explain the majority of nucleosome positions ('genomic code for nucleosome positioning'). Nonetheless, non-histone factors that bind DNA with high or low specificity, such as transcription factors or remodelling enzymes respectively and processes such as replication, transcription and the so-called 'statistical positioning' may be involved too. Recently, these models were tested for yeast by genome-wide reconstitution. DNA sequence preferences as probed by SGD (salt gradient dialysis) reconstitution generated many NDRs, but only few individual nucleosomes, at their proper positions, and no arrays. Addition of a yeast extract and ATP led to dramatically more in vivo-like nucleosome positioning, including regular arrays for the first time. This improvement depended essentially on the extract and ATP but not on transcription or replication. Nucleosome occupancy and close spacing were maintained around promoters, even at lower histone density, arguing for active packing of nucleosomes against the 5' ends of genes rather than statistical positioning. A first extract fractionation identified a direct, specific, necessary, but not sufficient role for the RSC (remodels the structure of chromatin) remodelling enzyme. Collectively, nucleosome positioning in yeast is actively determined by factors beyond intrinsic biophysics, and in steady-state rather than at equilibrium.

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

    PubMed Central

    Grov, Christian; Rendina, H. Jonathon; Moody, Raymond L.; Ventuneac, Ana

    2015-01-01

    Abstract 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

  5. Vocational rehabilitation of the socially disadvantaged long-term sick: inter-organizational co-operation between welfare state agencies.

    PubMed

    Lindqvist, R; Grape, O

    1999-03-01

    Vocational rehabilitation targeted to the socially disadvantaged long-term sick requires that the client keep in touch with a number of welfare state agencies, all of which have different regulations, conflicting goals and various types of benefits. This is an arduous and time-consuming task for clients with medical, social and labour market problems. Many of these clients run the risk of ending up in a no-man's land or being endlessly circulated between agencies because their problems do not correspond to the profile of the typical client. Both government and welfare workers see institutional co-operation between welfare state agencies as the remedy to such problems. This article, which is based on interviews with participants in fourteen cooperating projects, focuses on difficulties and opportunities experienced in such co-operation. It is concluded that such cooperation, when initiated in local settings and supported by local players, is a way of rejuvenating the existing Swedish model.

  6. A portable inhalational induction device provides co-operative induction of anaesthesia in preanaesthetic area for children

    PubMed Central

    Yun, Mi-Ja; Na, Hyo-Seok; Shin, Young Duck; Han, Jun-Sung; Hwang, Jung-Won; Kim, Chong Soo

    2010-01-01

    Background We introduce a new, simple portable inhalational induction device (PD) that provides co-operative inhalational induction of anaesthesia using N2O and subsequent sevoflurane in the preanaesthetic induction area in children. Methods Forty-five children (30 to 94 months old age, <35 kg) who were scheduled to undergo simple operations were assigned randomly to one of three regimens. Patients were encouraged by their parents to inhale N2O followed by sevoflurane (PD N2O-sevo group) or sevoflurane (PD sevo group) using a portable inhalational induction device in the preanaesthetic induction area until they were unable to respond to their names. They were then transferred to the operating room while maintaining inhalation of sevoflurane via the device. The control group underwent conventional inhalational induction in the operating room with the parents in attendance. Results Patients in the PD N2O-sevo group had a higher co-operative inhalation frequency than the patients in the PD sevo or the control group. Anaesthesia induction in the PD N2O-sevo and the PD sevo groups were faster than in the control group. Parent satisfaction score (0-100) was higher for the PD N2O-sevo group than for the control group. Conclusions A new portable inhalational induction device allows faster induction in co-operation with parents present in the preanaesthetic induction area compared to conventional inhalational induction in the unfamiliar operating room with the parents in attendance. PMID:20589175

  7. Evaluation development for a physical activity positive youth development program for girls.

    PubMed

    Ullrich-French, Sarah; Cole, Amy N; Montgomery, Anna K

    2016-04-01

    Girls on the Run (GOTR) is an after school program for girls in third through fifth grade which utilizes a physical activity based positive youth development curriculum that culminates with completing a 5K run. Unfortunately, there is little empirical data documenting GOTR participant changes that align with the curriculum and describe the evaluation process. Therefore, this study presents an evaluation of GOTR consisting of three main processes: curriculum content analysis and stakeholder focus groups (N=11) to identify key outcomes of the program; community-based participatory research to collaborate with program personnel to further identify important outcomes; and the design and pilot testing of an instrument (N=104) for assessing changes in the theoretically grounded outcomes over time. Findings demonstrated a positive collaborative process that led to important information to be used for an impact evaluation of Girls on the Run and for future evaluation development efforts for physical activity based positive youth development.

  8. 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…

  9. Towards an Understanding of Flow and Other Positive Experience Phenomena within Outdoor and Adventurous Activities.

    ERIC Educational Resources Information Center

    Boniface, Margaret R.

    2000-01-01

    People involved in adventurous activities frequently experience positive phenomena termed peak experience, peak performance, and "flow." Characteristics of these phenomena are compared, along with factors influencing the ability to experience such peak moments. Csikszentmihalyi's flow models are examined with regard to perceived levels…

  10. 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.

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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

  16. 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

  17. Neural substrates associated with evaluative processing during co-activation of positivity and negativity: a PET investigation.

    PubMed

    Jung, Young Chul; An, Suk Kyoon; Seok, Jeong Ho; Kim, Jae Seung; Oh, Seung Jun; Moon, Dae Hyuk; Kim, Jae-Jin

    2006-10-01

    Affective symmetries, such as the positivity offset and negativity bias, have been postulated to be attributable to distinct activation functions of the positive and negative affect systems. We investigated the neural substrates that are engaged when the positive and negative affect systems undergo parallel and integrative processing. Eleven subjects were scanned using H(2)(15)O PET during choosing the subjective feeling produced by a stimulation pair of pictures or words. Four different conditions were designed for contrast: pure positivity, pure negativity, positivity offset, and negativity bias. The dorsolateral prefrontal activation was associated with positivity offset and negativity bias condition, whereas the ventromedial prefrontal activation, together with limbic and subcortical activations, was associated with pure positivity and pure negativity condition. The results indicated that positivity offset and negativity bias are not merely due to asymmetric activations of the positive and negative systems, but integrative processing of higher neocortical levels is involved.

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

    PubMed

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

    2010-05-01

    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 the 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 on 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.

  19. Arm position influences the activation patterns of trunk muscles during trunk range-of-motion movements.

    PubMed

    Siu, Aaron; Schinkel-Ivy, Alison; Drake, Janessa Dm

    2016-10-01

    To understand the activation patterns of the trunk musculature, it is also important to consider the implications of adjacent structures such as the upper limbs, and the muscles that act to move the arms. This study investigated the effects of arm positions on the activation patterns and co-activation of the trunk musculature and muscles that move the arm during trunk range-of-motion movements (maximum trunk axial twist, flexion, and lateral bend). Fifteen males and fifteen females, asymptomatic for low back pain, performed maximum trunk range-of-motion movements, with three arm positions for axial twist (loose, crossed, abducted) and two positions for flexion and lateral bend (loose, crossed). Electromyographical data were collected for eight muscles bilaterally, and activation signals were cross-correlated between trunk muscles and the muscles that move the arms (upper trapezius, latissimus dorsi). Results revealed consistently greater muscle co-activation (higher cross-correlation coefficients) between the trunk muscles and upper trapezius for the abducted arm position during maximum trunk axial twist, while results for the latissimus dorsi-trunk pairings were more dependent on the specific trunk muscles (either abdominal or back) and latissimus dorsi muscle (either right or left side), as well as the range-of-motion movement. The findings of this study contribute to the understanding of interactions between the upper limbs and trunk, and highlight the influence of arm positions on the trunk musculature. In addition, the comparison of the present results to those of individuals with back or shoulder conditions may ultimately aid in elucidating underlying mechanisms or contributing factors to those conditions.

  20. [Antimicrobial spectrum of dalbavancin. Mechanism of action and in vitro activity against Gram-positive microorganisms].

    PubMed

    Cercenado, Emilia

    2017-01-01

    Because of the increase in bacterial resistance, there is a need for new antimicrobial agents. Dalbavancin is a semisynthetic glycopeptide that inhibits the late stages of bacterial cell wall synthesis in the same way as vancomycin, but in addition, its lipophilic side chain anchors dalbavancin to the cellular membrane and allows enhanced activity compared with that of vancomycin. Dalbavancin possesses a broad spectrum of in vitro activity against Gram-positive aerobic and anaerobic microorganisms, being 4-8 times more potent than vancomycin. The spectrum of dalbavancin includes staphylococci, enterococci, streptococci, and anaerobic Gram-positive cocci and bacilli. It is active against different species of multiresistant microorganisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant viridans streptococci and Streptococcus pneumoniae. Although it shows in vitro activity against Enterococcus spp., it is inactive against isolates expressing the VanA phenotype of vancomycin resistance. It also shows slow bactericidal activity against S. aureus, coagulase-negative staphylococci, and Streptococcus pyogenes. In general, the MIC90 (minimum inhibitory concentration 90%) against the majority of the microorganisms is 0.06mg/L and, more than 98% of the isolates that have been tested are inhibited at concentrations of ≤ 0.12mg/L. Dalbavancin is an interesting addition to the therapeutic armamentarium for the treatment of infections caused by Gram-positive microorganisms, including multidrug-resistant isolates.

  1. Theoretical analysis of the relationship between positive/negative cooperativity and enzyme activation/inhibition.

    PubMed

    Ge, Hao; Qian, Min

    2009-09-01

    Cooperativity is one of the "paradigms" in enzyme kinetics and molecular biology. But the classical textbook treatment of enzyme kinetics always indeed separates the concepts of positive/negative cooperativity from enzyme activation/inhibition, at least partially. Few theoretical analysis of their relationship has been discussed, although its experimental investigations might date back at least to 1970s. In the present paper, we try to apply the change of free energy as a connective parameter for investigating the relationship between positive/negative cooperativity and enzyme activation/inhibition through several classic equilibrium binding models. It is explicitly shown that the terms of positive/negative cooperativity could be equivalently regarded as enzyme activation/inhibition of the saturation function induced by the substrate molecule itself rather than any other additional effectors. Moreover, both the degree of cooperativity phenomenon and the degree of enzyme activation/inhibition monotonically increase with the change of free energy. Note that this result is quite different from the idea of relating cooperativity to the concepts of "substrate activation/inhibition", which is identified when at high substrate concentrations the reaction rate decreases instead of tending towards the maximum velocity, since it always needs a second substrate molecule.

  2. 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.

  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.

  4. Influence Of Scapular Position On The Core Musculature Activation In The Prone Plank Exercise.

    PubMed

    Cortell-Tormo, Juan M; García-Jaén, Miguel; Chulvi-Medrano, Iván; Hernández-Sánchez, Sergio; Lucas-Cuevas, Ángel G; Tortosa-Martínez, Juan

    2016-10-26

    Prone plank is a widely used exercise in core stability training. Research has shown that pelvic tilt plays an important role on the electromyographical (EMG) activation of core musculature. However, the influence of scapular position on EMG activation is currently unknown. Therefore, this study evaluated the influence of scapular position on the core muscles during a prone plank. Surface electromyography of the rectus abdominis (RA), external oblique (EO), internal oblique (IO) and erector spinae (ES) was collected in fifteen participants (10 men, 5 women). Four variations of the prone plank were evaluated: scapular abduction with anterior (ABANT) and posterior (ABRET) pelvic tilt; and scapular adduction with anterior (ADANT) and posterior (ADRET) pelvic tilt. Individual muscle EMG and overall EMG for each plank exercise was analyzed. Joint positions were controlled with a 2D kinematic analysis. Ratings of perceived effort (RPE) were also registered. ADRET resulted in higher overall EMG activity compared to ABANT (p=0.04) and ADANT (p=0.04). Moreover, ADRET resulted in greater EMG activity compared to ADANT, ABANT, and ABRET for EO (p=0.000; p=0.000; p=0.035), IO (p=0.000; p=0.000; p=0.005) and ES (p=0.019; p=0.001; p=0.014). Regarding RA, ADRET was significantly higher compared to ADANT (p=0.002) and ABANT (p=0.005). Finally, ADRET provoked a higher RPE compared to ABANT (p=0.000), ABRET (p=0.001) and ADANT (p=0.015). These findings demonstrate the influence of the scapular and pelvic position on the EMG response of the core muscle groups analyzed in this study, and highlight the greater contribution of these muscles to the postural stabilizing demands during posterior pelvic tilt positions, particularly when the scapulae are in adduction.

  5. Gaze and hand position effects on finger-movement-related human brain activation.

    PubMed

    Bédard, Patrick; Sanes, Jerome N

    2009-02-01

    Humans commonly use their hands to move and to interact with their environment by processing visual and proprioceptive information to determine the location of a goal-object and the initial hand position. It remains elusive, however, how the human brain fully uses this sensory information to generate accurate movements. In monkeys, it appears that frontal and parietal areas use and combine gaze and hand signals to generate movements, whereas in humans, prior work has separately assessed how the brain uses these two signals. Here we investigated whether and how the human brain integrates gaze orientation and hand position during simple visually triggered finger tapping. We hypothesized that parietal, frontal, and subcortical regions involved in movement production would also exhibit modulation of movement-related activation as a function of gaze and hand positions. We used functional MRI to measure brain activation while healthy young adults performed a visually cued finger movement and fixed gaze at each of three locations and held the arm in two different configurations. We found several areas that exhibited activation related to a mixture of these hand and gaze positions; these included the sensory-motor cortex, supramarginal gyrus, superior parietal lobule, superior frontal gyrus, anterior cingulate, and left cerebellum. We also found regions within the left insula, left cuneus, left midcingulate gyrus, left putamen, and right tempo-occipital junction with activation driven only by gaze orientation. Finally, clusters with hand position effects were found in the cerebellum bilaterally. Our results indicate that these areas integrate at least two signals to perform visual-motor actions and that these could be used to subserve sensory-motor transformations.

  6. Use of Cellular Decapping Activators by Positive-Strand RNA Viruses

    PubMed Central

    Jungfleisch, Jennifer; Blasco-Moreno, Bernat; Díez, Juana

    2016-01-01

    Positive-strand RNA viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral RNA translation and replication. In this review, we describe the versatile interaction of positive-strand RNA viruses and the 5′-3′ mRNA decay machinery with a focus on the viral subversion of decapping activators. This highly conserved viral trickery is exemplified with the plant Brome mosaic virus, the animal Flock house virus and the human hepatitis C virus. PMID:28009841

  7. 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…

  8. Brain activation related to combinations of gaze position, visual input, and goal-directed hand movements.

    PubMed

    Bédard, Patrick; Wu, Min; Sanes, Jerome N

    2011-06-01

    Humans reach to and acquire objects by transforming visual targets into action commands. How the brain integrates goals specified in a visual framework to signals into a suitable framework for an action plan requires clarification whether visual input, per se, interacts with gaze position to formulate action plans. To further evaluate brain control of visual-motor integration, we assessed brain activation, using functional magnetic resonance imaging. Humans performed goal-directed movements toward visible or remembered targets while fixating gaze left or right from center. We dissociated movement planning from performance using a delayed-response task and manipulated target visibility by its availability throughout the delay or blanking it 500 ms after onset. We found strong effects of gaze orientation on brain activation during planning and interactive effects of target visibility and gaze orientation on movement-related activation during performance in parietal and premotor cortices (PM), cerebellum, and basal ganglia, with more activation for rightward gaze at a visible target and no gaze modulation for movements directed toward remembered targets. These results demonstrate effects of gaze position on PM and movement-related processes and provide new information how visual signals interact with gaze position in transforming visual inputs into motor goals.

  9. Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity.

    PubMed

    Cheng, Hanyin; Ross, Jeremy A; Frost, Jeffrey A; Kirken, Robert A

    2008-04-01

    Janus tyrosine kinase 3 (Jak3) is essential for signaling by interleukin-2 (IL-2) family cytokines and proper immune function. Dysfunctional regulation of Jak3 may result in certain disease states. However, the molecular mechanisms governing Jak3 activation are not fully understood. In this study, we used a functional-proteomics approach to identify two novel tyrosine phosphorylation sites within Jak3, Y904 and Y939, which are conserved among Jak family proteins. By using phosphospecific antibodies, both residues were observed to be rapidly induced by stimulation of cells with IL-2 or other gammac cytokines. Mechanistic studies indicated that Y904 and Y939 regulate Jak3 activities. A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo, suggesting that phosphorylation of these previously unrecognized residues positively regulates Jak3 activity. Y904 and Y939 were required for optimal ATP usage by Jak3, while phosphorylation of Y939 preferentially promoted Stat5 activity in intact cells. Together, these findings demonstrate positive functional roles for two novel Jak3 phosphoregulatory sites which may be similarly important for other Jak family members. Identification of these sites also provides new therapeutic opportunities to modulate Jak3 function.

  10. An Analysis of Muscle Activities of Healthy Women during Pilates Exercises in a Prone Position.

    PubMed

    Kim, Bo-In; Jung, Ju-Hyeon; Shim, Jemyung; Kwon, Hae-Yeon; Kim, Haroo

    2014-01-01

    [Purpose] This study analyzed the activities of the back and hip muscles during Pilates exercises conducted in a prone position. [Subjects] The subjects were 18 healthy women volunteers who had practiced at a Pilates center for more than three months. [Methods] The subjects performed three Pilates exercises. To examine muscle activity during the exercises, 8-channel surface electromyography (Noraxon USA, Inc., Scottsdale, AZ) was used. The surface electrodes were attached to the bilateral latissimus dorsi muscle, multifidus muscle, gluteus maximus, and semitendinous muscle. Three Pilates back exercises were compared: (1) double leg kick (DLK), (2) swimming (SW), and (3) leg beat (LB). Electrical muscle activation was normalized to maximal voluntary isometric contraction. Repeated measures analysis of variance was performed to assess the differences in activation levels among the exercises. [Results] The activity of the multifidus muscle was significantly high for the SW (52.3±11.0, 50.9±9.8) and LB exercises(51.8±12.8, 48.3±13.9) and the activity of the semitendinosus muscle was higher for the LB exercise (49.2±8.7, 52.9±9.3) than for the DLK and SW exercises. [Conclusion] These results may provide basic material for when Pilates exercises are performed in a prone position and may be useful information on clinical Pilates for rehabilitation programs.

  11. Visualization of positive transcription elongation factor b (P-TEFb) activation in living cells.

    PubMed

    Fujinaga, Koh; Luo, Zeping; Schaufele, Fred; Peterlin, B Matija

    2015-01-16

    Regulation of transcription elongation by positive transcription elongation factor b (P-TEFb) plays a central role in determining the state of cell activation, proliferation, and differentiation. In cells, P-TEFb exists in active and inactive forms. Its release from the inactive 7SK small nuclear ribonucleoprotein complex is a critical step for P-TEFb to activate transcription elongation. However, no good method exists to analyze this P-TEFb equilibrium in living cells. Only inaccurate and labor-intensive cell-free biochemical assays are currently available. In this study, we present the first experimental system to monitor P-TEFb activation in living cells. We created a bimolecular fluorescence complementation assay to detect interactions between P-TEFb and its substrate, the C-terminal domain of RNA polymerase II. When cells were treated with suberoylanilide hydroxamic acid, which releases P-TEFb from the 7SK small nuclear ribonucleoprotein, they turned green. Other known P-TEFb-releasing agents, including histone deacetylase inhibitors, bromodomain and extraterminal bromodomain inhibitors, and protein kinase C agonists, also scored positive in this assay. Finally, we identified 5'-azacytidine as a new P-TEFb-releasing agent. This release of P-TEFb correlated directly with activation of human HIV and HEXIM1 transcription. Thus, our visualization of P-TEFb activation by fluorescent complementation assay could be used to find new P-TEFb-releasing agents, compare different classes of agents, and assess their efficacy singly and/or in combination.

  12. 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

  13. Bactericidal Activity and Mechanism of Photoirradiated Polyphenols against Gram-Positive and -Negative Bacteria.

    PubMed

    Nakamura, Keisuke; Ishiyama, Kirika; Sheng, Hong; Ikai, Hiroyo; Kanno, Taro; Niwano, Yoshimi

    2015-09-09

    The bactericidal effect of various types of photoirradiated polyphenols against Gram-positive and -negative bacteria was evaluated in relation to the mode of action. Gram-positive bacteria (Enterococcus faecalis, Staphylococcus aureus, and Streptococcus mutans) and Gram-negative bacteria (Aggregatibacter actinomycetemcomitans, Escherichia coli, and Pseudomonas aeruginosa) suspended in a 1 mg/mL polyphenol aqueous solution (caffeic acid, gallic acid, chlorogenic acid, epigallocatechin, epigallocatechin gallate, and proanthocyanidin) were exposed to LED light (wavelength, 400 nm; irradiance, 260 mW/cm(2)) for 5 or 10 min. Caffeic acid and chlorogenic acid exerted the highest bactericidal activity followed by gallic acid and proanthocyanidin against both Gram-positive and -negative bacteria. It was also demonstrated that the disinfection treatment induced oxidative damage of bacterial DNA, which suggests that polyphenols are incorporated into bacterial cells. The present study suggests that blue light irradiation of polyphenols could be a novel disinfection treatment.

  14. 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.

  15. Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position.

    PubMed

    Miyamoto, K; Yamamoto, Y; Kurita, M; Sakai, R; Konno, K; Sanae, F; Ohshima, T; Takagi, K; Hasegawa, T; Iwasaki, N

    1993-05-14

    Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2'-ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3-propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute

  16. 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

  17. False positive RNA binding activities after Ni-affinity purification from Escherichia coli.

    PubMed

    Milojevic, Tetyana; Sonnleitner, Elisabeth; Romeo, Alessandra; Djinović-Carugo, Kristina; Bläsi, Udo

    2013-06-01

    A His-tag is often added by means of recombinant DNA technology to a heterologous protein of interest, which is then over-produced in Escherchia coli and purified by one-step immobilized metal-affinity chromatography (IMAC). Owing to the presence of 24 histidines at the C-termini of the hexameric E. coli RNA chaperone Hfq, the protein co-purifies with His-tagged proteins of interest. As Hfq can bind to distinct RNA substrates with high affinity, its presence can obscure studies performed with (putative) RNA binding activities purified by IMAC. Here, we present results for a seemingly positive RNA-binding activity, exemplifying that false-positive results can be avoided if the protein of interest is either subjected to further purification step(s) or produced in an E. coli hfq- strain.

  18. Triazolopyridine ethers as potent, orally active mGlu2 positive allosteric modulators for treating schizophrenia.

    PubMed

    Higgins, Mendi A; Marcin, Lawrence R; Christopher Zusi, F; Gentles, Robert; Ding, Min; Pearce, Bradley C; Easton, Amy; Kostich, Walter A; Seager, Matthew A; Bourin, Clotilde; Bristow, Linda J; Johnson, Kim A; Miller, Regina; Hogan, John; Whiterock, Valerie; Gulianello, Michael; Ferrante, Meredith; Huang, Yanling; Hendricson, Adam; Alt, Andrew; Macor, John E; Bronson, Joanne J

    2017-01-15

    Triazolopyridine ethers with mGlu2 positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mGlu2 PAMs for the treatment of schizophrenia and merit further preclinical investigation.

  19. Participant Perceptions of Character Concepts in a Physical Activity-Based Positive Youth Development Program.

    PubMed

    Riciputi, Shaina; McDonough, Meghan H; Ullrich-French, Sarah

    2016-10-01

    Physical activity-based positive youth development (PYD) programs often aim to foster character development. This study examined youth perspectives of character development curricula and the impact these activities have on their lives within and beyond the program. This case study examined youth from low-income families in a physical activity-based summer PYD program that integrated one character concept (respect, caring, responsibility, trust) in each of 4 weeks. Participants (N = 24) included a cross section of age, gender, ethnicity, and past program experience. Semi-structured interviews were analyzed using inductive thematic analysis and constant comparative methods. Thirteen themes were grouped in four categories: building highquality reciprocal relationships; intrapersonal improvement; moral reasoning and understanding; and rejection, resistance, and compliance. The findings provide participant-centered guidance for understanding youth personal and social development through physical activity in ways that are meaningful to participants, which is particularly needed for youth in low-income communities with limited youth programming.

  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. 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

  2. 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.

  3. Modifications in activation of lower limb muscles as a function of initial foot position in cycling.

    PubMed

    Padulo, Johnny; Powell, Douglas W; Ardigò, Luca P; Viggiano, Davide

    2015-08-01

    Cyclic movements, such as walking/cycling, require the activity of spinal-circuits, the central-pattern-generators (CPG). To our knowledge little work has been done to investigate the activation of these circuits, e.g., the muscular and kinematic activity during cycling initiation. This study aims to detail the muscle output properties as a function of the initial lower limb-position using a simple cycling paradigm. Therefore, subjects were required to pedal on a cycle-ergometer in seated position starting at different-crank-angles (0-150°). Surface-electromyography was recorded from the gluteus major (GL), vastus lateralis (VL), and gastrocnemius medialis (GM), while crank position was recorded using a linear-encoder. Gluteus major peak-activity (PA) occurred at 65.0±12.4° when starting with 0° initial crank position (ICP), while occurred maximally at 110.5±2.9 when starting with 70° ICP. Vastus lateralis PA occurred at 40.7±8.8° with 0° ICP, whereas with 70° ICP PA occurred at 103.4±4.0°. Similarly, GM PA occurred at 112.0±10.7° with 0° ICP, whereas with 70° ICP PA occurred at 142.5±4.2° PA. Gluteus major and gastrocnemius medialis showed similar PA phase shifts, which may suggest they are controlled by same local circuitry, in agreement with their common spinal origin, i.e., motoneurons pool in S1-S2.

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

    PubMed Central

    Ley, Steven C.

    2016-01-01

    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

  5. Parvalbumin-Positive Inhibitory Interneurons Oppose Propagation But Favor Generation of Focal Epileptiform Activity.

    PubMed

    Sessolo, Michele; Marcon, Iacopo; Bovetti, Serena; Losi, Gabriele; Cammarota, Mario; Ratto, Gian Michele; Fellin, Tommaso; Carmignoto, Giorgio

    2015-07-01

    Parvalbumin (Pv)-positive inhibitory interneurons effectively control network excitability, and their optogenetic activation has been reported to block epileptic seizures. An intense activity in GABAergic interneurons, including Pv interneurons, before seizures has been described in different experimental models of epilepsy, raising the hypothesis that an increased GABAergic inhibitory signal may, under certain conditions, initiate seizures. It is therefore unclear whether the activity of Pv interneurons enhances or opposes epileptiform activities. Here we use a mouse cortical slice model of focal epilepsy in which the epileptogenic focus can be identified and the role of Pv interneurons in the generation and propagation of seizure-like ictal events is accurately analyzed by a combination of optogenetic, electrophysiological, and imaging techniques. We found that a selective activation of Pv interneurons at the focus failed to block ictal generation and induced postinhibitory rebound spiking in pyramidal neurons, enhancing neuronal synchrony and promoting ictal generation. In contrast, a selective activation of Pv interneurons distant from the focus blocked ictal propagation and shortened ictal duration at the focus. We revealed that the reduced ictal duration was a direct consequence of the ictal propagation block, probably by preventing newly generated afterdischarges to travel backwards to the original focus of ictal initiation. Similar results were obtained upon individual Pv interneuron activation by intracellular depolarizing current pulses. The functional dichotomy of Pv interneurons here described opens new perspectives to our understanding of how local inhibitory circuits govern generation and spread of focal epileptiform activities.

  6. Antioxidant activity via DPPH, gram-positive and gram-negative antimicrobial potential in edible mushrooms.

    PubMed

    Ahmad, Nisar; Mahmood, Fazal; Khalil, Shahid Akbar; Zamir, Roshan; Fazal, Hina; Abbasi, Bilal Haider

    2014-10-01

    Edible mushrooms (EMs) are nutritionally rich source of proteins and essential amino acids. In the present study, the antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial potential in EMs (Pleurotus ostreatus, Morchella esculenta, P. ostreatus (Black), P. ostreatus (Yellow) and Pleurotus sajor-caju) were investigated. The DPPH radical scavenging activity revealed that the significantly higher activity (66.47%) was observed in Morchella esculenta at a maximum concentration. Similarly, the dose-dependent concentrations (200, 400, 600, 800 and 1000 µg) were also used for other four EMs. Pleurotus ostreatus exhibited 36.13% activity, P. ostreatus (Black (B)) exhibited 30.64%, P. ostreatus (Yellow (Y)) exhibited 40.75% and Pleurotus sajor-caju exhibited 47.39% activity at higher concentrations. Furthermore, the antimicrobial potential were investigated for its toxicity against gram-negative bacterial strains (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Klebsiella pneumonia, Erwinia carotovora and Agrobacterium tumifaciens), gram-positive bacterial strains (Bacillus subtilis, Bacillus atrophaeus and Staphylococcus aureus) and a fungal strain (Candida albicans) in comparison with standard antibiotics. Antimicrobial screening revealed that the ethanol extract of P. ostreatus was active against all microorganism tested except E. coli. Maximum zone of inhibition (13 mm) was observed against fungus and A. tumifaciens. P. sajor-caju showed best activities (12.5 mm) against B. subtilis, B. atrophaeus and K. pneumonia. P. ostreatus (Y) showed best activities against P. aeroginosa (21.83 mm), B. atrophaeus (20 mm) and C. albicans (21 mm). P. ostreatus (B) exhibited best activities against C. albicans (16 mm) and slightly lower activities against all other microbes except S. typhi. M. esculenta possess maximum activities in terms of inhibition zone against all microorganisms tested except S. typhi.

  7. Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia Alcocer

    2015-03-01

    There are several reports which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action of steroid derivatives at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, two dihydrotestosterone derivatives (compounds 5 and 10) were synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. In the first stage, the Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the steroid derivatives. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the compound 5 was evaluated by measuring left ventricular pressure in absence or presence of following compounds; nifedipine, flutamide, indomethacin, prazosin, isoproterenol, propranolol and metoprolol. The results showed that the compound 5 significantly increased the perfusion pressure and coronary resistance in comparison with dihydrotestosterone, compound 10 and the control conditions. Other data indicate that 5 increase left ventricular pressure in a dose-dependent manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited only by propranolol or metoprolol at a dose of 1 nM. These data suggest that positive inotropic activity induced by the compound 5 is through β1-adrenergic receptor however, this effect was independent of cAMP levels. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

  8. 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

  9. 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

  10. LTI system order reduction approach based on asymptotical equivalence and the Co-operation of biology-related algorithms

    NASA Astrophysics Data System (ADS)

    Ryzhikov, I. S.; Semenkin, E. S.; Akhmedova, Sh A.

    2017-02-01

    A novel order reduction method for linear time invariant systems is described. The method is based on reducing the initial problem to an optimization one, using the proposed model representation, and solving the problem with an efficient optimization algorithm. The proposed method of determining the model allows all the parameters of the model with lower order to be identified and by definition, provides the model with the required steady-state. As a powerful optimization tool, the meta-heuristic Co-Operation of Biology-Related Algorithms was used. Experimental results proved that the proposed approach outperforms other approaches and that the reduced order model achieves a high level of accuracy.

  11. Cdc42 activation couples spindle positioning to first polar body formation in oocyte maturation.

    PubMed

    Ma, Chunqi; Benink, Héléne A; Cheng, Daye; Montplaisir, Véronique; Wang, Ling; Xi, Yanwei; Zheng, Pei-Pei; Bement, William M; Liu, X Johné

    2006-01-24

    During vertebrate egg maturation, cytokinesis initiates after one pole of the bipolar metaphase I spindle attaches to the oocyte cortex, resulting in the formation of a polar body and the mature egg. It is not known what signal couples the spindle pole positioning to polar body formation. We approached this question by drawing an analogy to mitotic exit in budding yeast, as asymmetric spindle attachment to the appropriate cortical region is the common regulatory cue. In budding yeast, the small G protein Cdc42 plays an important role in mitotic exit following the spindle pole attachment . We show here that inhibition of Cdc42 activation blocks polar body formation. The oocytes initiate anaphase but fail to properly form and direct a contractile ring. Endogenous Cdc42 is activated at the spindle pole-cortical contact site immediately prior to polar body formation. The cortical Cdc42 activity zone, which directly overlays the spindle pole, is circumscribed by a cortical RhoA activity zone; the latter defines the cytokinetic contractile furrow . As the RhoA ring contracts during cytokinesis, the Cdc42 zone expands, maintaining its complementary relationship with the RhoA ring. Cdc42 signaling may thus be an evolutionarily conserved mechanism that couples spindle positioning to asymmetric cytokinesis.

  12. Laser-Machined Shape Memory Alloy Sensors for Position Feedback in Active Catheters

    PubMed Central

    Tung, Alexander T.; Park, Byong-Ho; Liang, David H.; Niemeyer, Günter

    2008-01-01

    Catheter-based interventions are a form of minimally invasive surgery that can decrease hospitalization time and greatly lower patient morbidity compared to traditional methods. However, percutaneous catheter procedures are hindered by a lack of precise tip manipulation when actuation forces are transmitted over the length of the catheter. Active catheters with local shape-memory-alloy (SMA) actuation can potentially provide the desired manipulation of a catheter tip, but hysteresis makes it difficult to control the actuators. A method to integrate small-volume, compliant sensors on an active catheter to provide position feedback for control would greatly improve the viability of SMA-based active catheters. In this work, we describe the design, fabrication, and performance of resistance-based position sensors that are laser-machined from superelastic SMA tubing. Combining simple material models and rapid prototyping, we can develop sensors of appropriate stiffness and sensitivity with simple modifications in sensor geometry. The sensors exhibit excellent linearity over the operating range and are designed to be easily integrated onto an active catheter substrate. PMID:19759806

  13. Impact of the initial tropospheric zenith path delay on precise point positioning convergence during active conditions

    NASA Astrophysics Data System (ADS)

    Kalita, J. Z.; Rzepecka, Z.

    2017-04-01

    Tropospheric delay is one of the key factors that influence the convergence time of the precise point positioning (PPP) method. Current models do not allow for the fixing of the zenith path delay tropospheric parameter, leaving the difference between nominal and final value to the estimation process. Here, we present an analysis of several PPP result-sets using the tropospheric parameter’s nominal value adopted from models: VMF1, GPT2w, MOPS, and ZERO-WET. The last variant assumes a zero value for the initial wet part of the zenith delay. The PPP results are subtracted from a solution based on the final tropospheric product from the International GNSS Service (IGS). Several days exhibiting the most active tropospheric conditions were selected for each of the 7 stations located in the mid-latitude Central European region. During the active days, application of the VMF1 model increases the resulting height component’s quality by about 33–36% when compared to the GPT2w and MOPS. The respective improvement in VMF1 latitude and longitude components is 27% and 15%. The average relative deterioration in the result standard deviations between active and calm tropospheric conditions reaches about 20–30% of the former. We discuss the impact of the initial tropospheric parameter’s variance and bias on positioning. In addition, we compare the results with those of other studies over the impact of active tropospheric conditions on the PPP method.

  14. 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.

  15. Active and Progressive Exoskeleton Rehabilitation Using Multisource Information Fusion From EMG and Force-Position EPP.

    PubMed

    Fan, Yuanjie; Yin, Yuehong

    2013-12-01

    Although exoskeletons have received enormous attention and have been widely used in gait training and walking assistance in recent years, few reports addressed their application during early poststroke rehabilitation. This paper presents a healthcare technology for active and progressive early rehabilitation using multisource information fusion from surface electromyography and force-position extended physiological proprioception. The active-compliance control based on interaction force between patient and exoskeleton is applied to accelerate the recovery of the neuromuscular function, whereby progressive treatment through timely evaluation contributes to an effective and appropriate physical rehabilitation. Moreover, a clinic-oriented rehabilitation system, wherein a lower extremity exoskeleton with active compliance is mounted on a standing bed, is designed to ensure comfortable and secure rehabilitation according to the structure and control requirements. Preliminary experiments and clinical trial demonstrate valuable information on the feasibility, safety, and effectiveness of the progressive exoskeleton-assisted training.

  16. d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study

    PubMed Central

    Bai, Defa; Yu, Siming; Zhong, Shenghui; Zhao, Bingxin; Qiu, Shaoling; Chen, Jianwei; Lunagariya, Jignesh; Liao, Xiaojian; Xu, Shihai

    2017-01-01

    Galaxamide, an extract from Galaxaura filamentosa, is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG2), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG2 cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG2 cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG2 cells. PMID:28287429

  17. d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study.

    PubMed

    Bai, Defa; Yu, Siming; Zhong, Shenghui; Zhao, Bingxin; Qiu, Shaoling; Chen, Jianwei; Lunagariya, Jignesh; Liao, Xiaojian; Xu, Shihai

    2017-03-10

    Galaxamide, an extract from Galaxaura filamentosa, is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG₂), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG₂ cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG₂ cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG₂ cells.

  18. 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

  19. Influence of Catalase Activity on Resistance of Coagulase-positive Staphylococci to Hydrogen Peroxide1

    PubMed Central

    Amin, V. M.; Olson, N. F.

    1968-01-01

    Catalase activities of intact cells and cell-free extracts of coagulase-positive staphylococcal cultures 105B and 558D isolated from milk, culture 25042 from a clinical source, and Staphylococcus aureus 196E were determined at 32.2 C. Cultures were treated with 0.025 and 0.05% hydrogen peroxide at 37.8 and 54.4 C and without hydrogen peroxide at 54.4 C to determine the relationship between catalase activity and resistance to these treatments. The relationship held true for cultures 105B and 196E; culture 105B had the lowest catalase activity and lowest resistance to H2O2 at 37.8 C, whereas S. aureus 196E possessed a high catalase activity and was most resistant at 37.8 C. Catalase activities of cell-free extracts of cultures 25042, 558, and 196E were similar, but resistance to H2O2 at 37.8 C was greater for culture 196E. The lower resistance of culture 25042 was related to low catalase activities of whole cells of this culture, which were only one-third that of whole cells of culture 196E. Culture 558 was least resistant to heat treatment at 54.4 C and showed the greatest sensitivity to added H2O2 at this temperature. PMID:5645413

  20. Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart.

    PubMed

    Sanae, F; Ohmae, S; Kurita, M; Sawanishi, H; Takagi, K; Miyamoto, K

    1995-10-01

    Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.

  1. Effects of hand and knee positions on muscular activity during trunk extension exercise with the Roman chair.

    PubMed

    Park, Se-yeon; Yoo, Won-gyu

    2014-12-01

    This experimental study was performed to investigate the effects of hand and knee positions on muscular activity during back extension exercises with the Roman chair. Eighteen asymptomatic male amateur athletes performed four prone back extension exercises with two hand positions (crossed-arms and behind-the-head), and two knee positions (extended knee and 90° flexed knee). Surface electromyography (sEMG) was performed to collect data from the lower trapezius (LT), latissimus dorsi (LD), erector spinae in the T12 paraspinal region (ES-T12), erector spinae at the L3 level (ES-L3), gluteus maximus (GM), and biceps femoris (BF). Two-way repeated analysis of variance with two within-subject factors (two hand positions and two knee positions) was used to determine the significance of differences between the exercise conditions, and which hand and knee positions resulted in greater activation with exercise variation. The root mean square sEMG values were normalized using the maximum voluntary isometric contraction (MVIC) and represented as the % of the maximum EMG (%mEMG). There was no significant interaction between knee and hand positions in the %mEMG data. The results showed that the hand position affected the normalized activation of LT; the behind-the-head position resulted in significantly greater muscle activation than the crossed-arms hand position (P<0.05). The activations of the LD, ES-T10, ES-L4, and GM were greater in the 90° flexed-knee position compared to the extended-knee position (P<0.05). Although back extension exercise using the Roman chair has been shown to effectively activate the extensor musculature, our results indicated that changing the knee and hand positions could activate specific muscles differently. To achieve greater activation of trunk extensor muscle during extension exercise with the Roman chair, the flexed-knee position is a useful means of increasing resistance.

  2. 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

  3. Active tuberculosis among Iraqi schoolchildren with positive skin tests and their household contacts.

    PubMed

    Al Kubaisy, W; Al Dulayme, A; Hashim, D S

    2003-07-01

    In a prospective cohort study in Iraq, schoolchildren with a positive tuberculin skin test during the nationwide survey in 2000 were followed up in 2002 to determine prevalence of latent tuberculosis (TB) infection and risk factors among household contacts. Of 205 children, 191 remained skin-test positive in 2002. Based on X-ray and clinical examination, 9 children (4.4%) were active TB cases. Among 834 household contacts, there were 144 new TB cases, giving a cumulative incidence of 17.3%. Risk factors for TB among household contacts were: age > or = 15 years; technical/professional job; smoking; low body mass index; diabetes mellitus; steroid therapy; and closeness of contact with the index cases. Based on past history of TB in index children and their contacts, 77.2% of new TB cases were attributable to household contacts.

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

    PubMed

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

    2015-09-01

    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.

  5. HIV-Positive Men Sexually Active with Women: Sexual Behaviors and Sexual Risks

    PubMed Central

    Lee, Gunjeong; Howard, Joyce Moon; Caban, Maria; Abramson, David; Messeri, Peter

    2006-01-01

    This study examines patterns of sexual behavior, sexual relating, and sexual risk among HIV-positive men sexually active with women. A total of 278 HIV-positive men were interviewed every 6–12 months between 1994 and 2002 and reported considerable variability in sexual behaviors over time. Many were not sexually active at all for months at a time; many continued to have multiple female and at times male partners. Over one-third of the cohort had one or more periods when they had engaged in unprotected sex with a female partner who was HIV-negative or status unknown (unsafe sex). Periods of unsafe sex alternated with periods of safer sex. Contextual factors such as partner relations, housing status, active drug use, and recently exchanging sex showed the strongest association with increased odds of unsafe sex. A number of predictors of unsafe sex among African American men were not significant among the Latino sub-population, suggesting race/ethnic differences in factors contributing to heterosexual transmission. Implications for prevention interventions are discussed. PMID:16770702

  6. Does cue context matter? Examining the specificity of cue-related activation of positive and negative alcohol expectancies.

    PubMed

    Wardell, Jeffrey D; Read, Jennifer P

    2013-12-01

    Consistent with the Encoding Specificity principle, positive alcohol expectancies may be activated by cues in drinking contexts because they are more closely associated with these cues in memory than are negative expectancies. However, there is little research examining the specificity of cue-induced alcohol expectancy activation. This study investigated the relative activation of positive and negative expectancies in response to positive and negative cue contexts. We also examined whether these effects were stronger for heavier and more problematic drinkers. College student drinkers were randomly assigned to listen to vignettes describing either positive or negative drinking scenarios (cue exposure). Participants also completed an implicit measure of alcohol expectancy activation (modified Stroop task) both before and after the cue exposure, as well as self-report measures of alcohol use and alcohol-related problems. We found that alcohol-related problems moderated the effects of cue condition on expectancy activation, such that specific activation of positive relative to negative expectancies in response to positive cues was observed only for drinkers with higher levels of alcohol problems. No differences in activation of positive versus negative expectancies were observed for more problematic drinkers in the negative cue condition or for less problematic drinkers in either cue condition. The results are partially consistent with the Encoding Specificity principle, showing that positive contextual cues can selectively activate positive alcohol expectancies for more problematic drinkers. Findings may have implications for interventions that target automatic expectancy processes, suggesting potential utility in targeting specific expectancies in specific contexts.

  7. Structure-activity relationships of nonisomerizable derivatives of tamoxifen: importance of hydroxyl group and side chain positioning for biological activity.

    PubMed

    Murphy, C S; Parker, C J; McCague, R; Jordan, V C

    1991-03-01

    The antiestrogen tamoxifen [(Z)-1(p-beta-dimethylaminoethoxy-phenyl)-1,2-diphenylbut-1-ene] is an effective anticancer agent against estrogen receptor (ER)-positive breast cancer. The alkylaminoethane side chain is essential for antiestrogenic activity, but the potency of the antiestrogen can be increased by para hydroxylation of the phenyl ring on carbon 1 of but-1-ene. This compound, 4-hydroxytamoxifen, is a metabolite of tamoxifen and has a very high binding affinity for ER [J. Endocrinol. 75:305-316 (1977)] because the hydroxyl is located in the equivalent position as the 3-phenolic hydroxyl of 17 beta-estradiol. In this study, we have examined the relationship between the relative positions of the hydroxyl and the alkyl-aminoethane side chain and the pharmacological activity of the ligand. A fixed seven-membered ring derivative of the triphenylethylene was used to prevent isomerization. All compounds were tested, with and without 17 beta-estradiol, for their effects on the growth of estrogen-responsive T47D and MCF-7 human breast cancer cells in vitro. The growth of MDA-MB-231 ER-negative breast cancer cells was not affected by any of the compounds tested, at a concentration (1 microM) that had a profound estrogenic or antiestrogenic action in ER-positive cell lines. The relative binding affinity of the compounds was determined using rat uterine ER and was found to be consistent with the observed potencies in vitro. The compounds found to be antiestrogens in vitro were antiestrogenic against estradiol (0.08 micrograms daily) in the 3-day immature rat uterine weight test. All compounds were partial agonists in vivo. In general, the estrogenic and antiestrogenic results obtained in vivo were consistent with the potency estimates obtained with the breast cancer cells in vitro. The results of this extensive structure-activity relationship study demonstrate that the substitution for 4-hydroxytamoxifen appears to be optimal to produce a potent antiestrogen; all

  8. 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

  9. New Positive Ca2+-Activated K+ Channel Gating Modulators with Selectivity for KCa3.1

    PubMed Central

    Coleman, Nichole; Brown, Brandon M.; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M.; Valero, Marta Sofia; Köhler, Ralf

    2014-01-01

    Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K+ channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1−/− mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation. PMID:24958817

  10. Small Molecule Positive Allosteric Modulation of TRPV1 Activation by Vanilloids and Acidic pHS⃞

    PubMed Central

    Kaszas, Krisztian; Keller, Jason M.; Coddou, Claudio; Mishra, Santosh K.; Hoon, Mark A.; Stojilkovic, Stanko; Jacobson, Kenneth A.

    2012-01-01

    Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a high-conductance, nonselective cation channel strongly expressed in nociceptive primary afferent neurons of the peripheral nervous system and functions as a multimodal nociceptor gated by temperatures greater than 43°C, protons, and small-molecule vanilloid ligands such as capsaicin. The ability to respond to heat, low pH, vanilloids, and endovanilloids and altered sensitivity and expression in experimental inflammatory and neuropathic pain models made TRPV1 a major target for the development of novel, nonopioid analgesics and resulted in the discovery of potent antagonists. In human clinical trials, observations of hyperthermia and the potential for thermal damage by suppressing the ability to sense noxious heat suggested that full-scale blockade of TRPV1 function can be counterproductive and subtler pharmacological approaches are necessary. Here we show that the dihydropyridine derivative 4,5-diethyl-3-(2-methoxyethylthio)-2-methyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS1477) behaves as a positive allosteric modulator of both proton and vanilloid activation of TRPV1. Under inflammatory-mimetic conditions of low pH (6.0) and protein kinase C phosphorylation, addition of MRS1477 further increased sensitivity of already sensitized TPRV1 toward capsaicin. MRS1477 does not affect inhibition by capsazepine or ruthenium red and remains effective in potentiating activation by pH in the presence of an orthosteric vanilloid antagonist. These results indicate a distinct site on TRPV1 for positive allosteric modulation that may bind endogenous compounds or novel pharmacological agents. Positive modulation of TRPV1 sensitivity suggests that it may be possible to produce a selective analgesia through calcium overload restricted to highly active nociceptive nerve endings at sites of tissue damage and inflammation. PMID:22005042

  11. Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.

    PubMed

    Figueroa-Valverde, L; Díaz-Cedillo, F; García-Cervera, E; Pool Gómez, E; López-Ramos, M; Rosas-Nexticapa, M; Martinez-Camacho, R

    2013-10-01

    Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

  12. ALDH enzymatic activity and CD133 positivity and response to chemotherapy in ovarian cancer patients.

    PubMed

    Ricci, Francesca; Bernasconi, Sergio; Porcu, Luca; Erba, Eugenio; Panini, Nicolò; Fruscio, Robert; Sina, Federica; Torri, Valter; Broggini, Massimo; Damia, Giovanna

    2013-01-01

    The prognostic/predictive role of both CD133 and Aldehyde dehydrogenase (ALDH) expression in human ovarian cancer remains elusive. This is an observational study that investigated the expression of CD133 and of ALDH enzymatic activity in fresh ovarian cancer samples and their association with different clinic-pathological patient' characteristics and explored their possible predictive/prognostic role. We analyzed the expression of CD133 and ALDH enzymatic activity in 108 human ovarian cancer samples. We found that among the total patients analyzed, 13% of them was completely negative for ALDH activity and 26% was negative for CD133 staining. Both markers were variably expressed within the samples and when both studied in the same tumor sample, no statistically significant correlation between ALDH enzymatic activity and CD133 expression was found. No statistical significant correlation was found also between the percentage values of positive ALDH and CD133 cells and the number of serial passages patient's cultures underwent, suggesting that these markers do not confer by themselves a self-renewal growth advantage to the cultures. Lower levels of CD133 were associated with higher tumor grade. No correlation with response to therapy, progression free survival and overall survival was found. Our data suggest that neither ALDH enzymatic activity nor CD133 expression provide additional predictive/prognostic information in ovarian cancer patients.

  13. HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation.

    PubMed

    Karamichali, Eirini; Foka, Pelagia; Tsitoura, Eliza; Kalliampakou, Katerina; Kazazi, Dorothea; Karayiannis, Peter; Georgopoulou, Urania; Mavromara, Penelope

    2014-08-01

    Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial. In this report, we confirmed previous studies showing that NS5A down-regulates IRES activity in HepG2 but not in Huh7 cells suggesting that the NS5A effect on HCV IRES is cell-type dependent. Additionally, we provide strong evidence that activated PKR up-regulates the IRES activity while silencing of endogenous PKR had the opposite effect. Furthermore, we present data indicating that the NS5A-mediated inhibitory effect on IRES-dependent translation could be linked with the PKR inactivation. Finally, we show that NS5A from GBV-C but not from GBV-B down-regulates HCV IRES activity in the absence or the presence of PKR over expression. Notably, HCV and GBV-C but not GBV-B NS5A contains a previously identified PKR interacting protein domain.

  14. Co-operation, Competition and Crowding: A Discrete Framework Linking Allee Kinetics, Nonlinear Diffusion, Shocks and Sharp-Fronted Travelling Waves.

    PubMed

    Johnston, Stuart T; Baker, Ruth E; McElwain, D L Sean; Simpson, Matthew J

    2017-02-14

    Invasion processes are ubiquitous throughout cell biology and ecology. During invasion, individuals can become isolated from the bulk population and behave differently. We present a discrete, exclusion-based description of the birth, death and movement of individuals. The model distinguishes between individuals that are part of, or are isolated from, the bulk population by imposing different rates of birth, death and movement. This enables the simulation of various co-operative or competitive mechanisms, where there is either a positive or negative benefit associated with being part of the bulk population, respectively. The mean-field approximation of the discrete process gives rise to 22 different classes of partial differential equation, which can include Allee kinetics and nonlinear diffusion. Here we examine the ability of each class of partial differential equation to support travelling wave solutions and interpret the long time behaviour in terms of the individual-level parameters. For the first time we show that the strong Allee effect and nonlinear diffusion can result in shock-fronted travelling waves. We also demonstrate how differences in group and individual motility rates can influence the persistence of a population and provide conditions for the successful invasion of a population.

  15. Co-operation, Competition and Crowding: A Discrete Framework Linking Allee Kinetics, Nonlinear Diffusion, Shocks and Sharp-Fronted Travelling Waves

    PubMed Central

    Johnston, Stuart T.; Baker, Ruth E.; McElwain, D. L. Sean; Simpson, Matthew J.

    2017-01-01

    Invasion processes are ubiquitous throughout cell biology and ecology. During invasion, individuals can become isolated from the bulk population and behave differently. We present a discrete, exclusion-based description of the birth, death and movement of individuals. The model distinguishes between individuals that are part of, or are isolated from, the bulk population by imposing different rates of birth, death and movement. This enables the simulation of various co-operative or competitive mechanisms, where there is either a positive or negative benefit associated with being part of the bulk population, respectively. The mean-field approximation of the discrete process gives rise to 22 different classes of partial differential equation, which can include Allee kinetics and nonlinear diffusion. Here we examine the ability of each class of partial differential equation to support travelling wave solutions and interpret the long time behaviour in terms of the individual-level parameters. For the first time we show that the strong Allee effect and nonlinear diffusion can result in shock-fronted travelling waves. We also demonstrate how differences in group and individual motility rates can influence the persistence of a population and provide conditions for the successful invasion of a population. PMID:28195135

  16. Co-operation, Competition and Crowding: A Discrete Framework Linking Allee Kinetics, Nonlinear Diffusion, Shocks and Sharp-Fronted Travelling Waves

    NASA Astrophysics Data System (ADS)

    Johnston, Stuart T.; Baker, Ruth E.; McElwain, D. L. Sean; Simpson, Matthew J.

    2017-02-01

    Invasion processes are ubiquitous throughout cell biology and ecology. During invasion, individuals can become isolated from the bulk population and behave differently. We present a discrete, exclusion-based description of the birth, death and movement of individuals. The model distinguishes between individuals that are part of, or are isolated from, the bulk population by imposing different rates of birth, death and movement. This enables the simulation of various co-operative or competitive mechanisms, where there is either a positive or negative benefit associated with being part of the bulk population, respectively. The mean-field approximation of the discrete process gives rise to 22 different classes of partial differential equation, which can include Allee kinetics and nonlinear diffusion. Here we examine the ability of each class of partial differential equation to support travelling wave solutions and interpret the long time behaviour in terms of the individual-level parameters. For the first time we show that the strong Allee effect and nonlinear diffusion can result in shock-fronted travelling waves. We also demonstrate how differences in group and individual motility rates can influence the persistence of a population and provide conditions for the successful invasion of a population.

  17. 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.

  18. 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…

  19. The Development of Co-Operation and Competition in Japanese Public Schools: Two National Surveys.

    ERIC Educational Resources Information Center

    Shwalb, Barbara J.; Shwalb, David W.

    1985-01-01

    Japanese school teachers provided examples of cooperative and competitive student behaviors in order to construct rating scales. Further ranking and factor analysis resulted in nine competitive and eight cooperative items. Age differences are discussed, as well as the Japanese society's encouragement of cooperative activities. The items are…

  20. Report to the Government of Zambia on Co-Operative Education.

    ERIC Educational Resources Information Center

    International Labour Office, Geneva (Switzerland).

    This 1-year study was undertaken in the Reupublic of Zambia to survey and analyze needs in cooperative education and training and to plan and execute immediate courses with detailed curricula in this area. A brief history of Zambian cooperative societies and a description of the expert's study activities are followed by conclusions and…

  1. Optimization of actuator and sensor positions for an active noise reduction system

    NASA Astrophysics Data System (ADS)

    Böhme, Sten; Sachau, Delf; Breitbach, Harald

    2006-03-01

    Different systems and strategies have been invented in order to reduce the noise level inside the fuselage of aircrafts. First of all passive methods like adding materials with high damping or vibration absorbing qualities were used. Due to mass reduction as a major aspect in aircraft design a lot of research is focused on active noise reduction (ANR). The level of attenuation gained by an ANR - system is depending on several attributes of the system like hardware and software in use. Another important parameter, which has a great impact on the performance, is the positioning of the actuators and sensors. Because of the high number of possible arrangements of actuators and sensors in three dimensional spaces, it is almost impossible to determine the optimal positions by experimental work. Therefore numerical optimization is applied. In this paper a hybrid evolutionary algorithm is introduced for the calculation of appropriate configurations for a fixed number of actuator and sensors out of a high number of possible positions for an ANR - system within a military aircraft. The presented COSA - algorithm (cooperative simulated annealing) connects qualities of two well known optimization algorithms, the simulated annealing (SA) and genetic algorithm (GA). A general description of the algorithm and the acoustical basics will be provided together with an overview of the results.

  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. Nucleophilic activation by positioning in phosphoryl transfer catalyzed by nucleoside diphosphate kinase.

    PubMed

    Admiraal, S J; Schneider, B; Meyer, P; Janin, J; Véron, M; Deville-Bonne, D; Herschlag, D

    1999-04-13

    The nonenzymatic reaction of ATP with a nucleophile to generate ADP and a phosphorylated product proceeds via a dissociative transition state with little bond formation to the nucleophile. Consideration of the dissociative nature of the nonenzymatic transition state leads to the following question: To what extent can the nucleophile be activated in enzymatic phosphoryl transfer? We have addressed this question for the NDP kinase reaction. A mutant form of the enzyme lacking the nucleophilic histidine (H122G) can be chemically rescued for ATP attack by imidazole or other exogenous small nucleophiles. The ATP reaction is 50-fold faster with the wild-type enzyme, which has an imidazole nucleophile positioned for reaction by a covalent bond, than with H122G, which employs a noncovalently bound imidazole nucleophile [(kcat/KM)ATP]. Further, a 4-fold advantage for imidazole positioned in the nucleophile binding pocket created by the mutation is suggested from comparison of the reaction of H122G and ATP with an imidazole versus a water nucleophile, after correction for the intrinsic reactivities of imidazole and water toward ATP in solution. X-ray structural analysis shows no detectable rearrangement of the residues surrounding His 122 upon mutation to Gly 122. The overall rate effect of approximately 10(2)-fold for the covalent imidazole nucleophile relative to water is therefore attributed to positioning of the nucleophile with respect to the reactive phosphoryl group. This is underscored by the more deleterious effect of replacing ATP with AlphaTauPgammaS in the wild-type reaction than in the imidazole-rescued mutant reaction, as follows. For the wild-type, AlphaTauPgammaS presumably disrupts positioning between nucleophile and substrate, resulting in a large thio effect of 300-fold, whereas precise alignment is already disrupted in the mutant because there is no covalent bond to the nucleophile, resulting in a smaller thio effect of 10-fold. In summary, the results

  4. Positively charged gold nanoparticles synthesized by electrochemically active biofilm--a biogenic approach.

    PubMed

    Khan, Mohammad Mansoob; Kalathil, S; Han, Thi Hiep; Lee, Jintae; Cho, Moo Hwan

    2013-09-01

    Positively charged gold nanoparticles [(+) AuNPs] of 5-20 nm were synthesized by using electrochemically active biofilm (EAB) formed on a stainless steel mesh, within 30 minutes, in aqueous solution containing HAuCl4 as a precursor and sodium acetate as an electron donor. Electrochemically active bacteria present on biofilm oxidize the sodium acetate by producing electrons. Simultaneously, stainless steel also provides electrons because of the Cl- ions penetration into the stainless steel. Combined effect of both the EAB and stainless steel mesh enhances the availability of electrons for the reduction of Au3+ in the solution, which makes this synthesis efficient and fast. Therefore, small size, positively charged (+32.72 mV), monodispersed, controlled, easy separation and extracellular synthesis of (+) AuNPs makes this protocol highly significant. As-synthesized AuNPs were characterized by UV-vis, DLS, XRD, TEM, HRTEM, EDX and SAED. (+) AuNPs shows remarkable enhancement in the rate of reduction of methyl orange by NaBH4 because of the electron relay effect.

  5. Positive Feedback Genetic Circuit Incorporating a Constitutively Active Mutant Gal3 into Yeast GAL Induction System.

    PubMed

    Ryo, Shintaro; Ishii, Jun; Matsuno, Toshihide; Nakamura, Yasuyuki; Matsubara, Daiki; Tominaga, Masahiro; Kondo, Akihiko

    2017-03-27

    The GAL expression system is the most frequently used induction technique in the yeast Saccharomyces cerevisiae. Here we report a simple but powerful genetic circuit for use with the GAL induction system. Briefly, an artificial positive feedback circuit was incorporated into the GAL regulatory network. We selected green fluorescent protein (GFP) as a reporter of GAL1 induction, and designed a strain that expressed a constitutively active Gal3 mutant protein (Gal3(c)) under control of the GAL10 promoter. In the resulting strain, GAL1 and GAL10 promoters regulate the expression of GFP and GAL3(c), respectively. Because Gal3(c) sequesters the Gal80 repressor away from the Gal4 transcriptional activator in the same manner as the galactose-bound Gal3, the expressed Gal3(c) protein provokes further expression of GFP and Gal3(c), yielding further enhancement of GAL induction. Thus, this GAL3(c)-mediated positive feedback circuit permits substantially enriched induction of a target gene at extremely low concentrations, or even in the absence, of galactose, while maintaining the strict glucose-mediated repression of the target.

  6. 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

    2015-09-28

    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.

  7. 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

  8. 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.

  9. 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.

  10. Nur1 Dephosphorylation Confers Positive Feedback to Mitotic Exit Phosphatase Activation in Budding Yeast

    PubMed Central

    Godfrey, Molly; Kuilman, Thomas; Uhlmann, Frank

    2015-01-01

    Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle. PMID:25569132

  11. Positive Regulation of Interleukin-2 Expression by a Pseudokinase, Tribbles 1, in Activated T Cells.

    PubMed

    Miyajima, Chiharu; Itoh, Yuka; Inoue, Yasumichi; Hayashi, Hidetoshi

    2015-01-01

    Tribbles 1 (TRB1), a member of the Tribbles family, is a pseudokinase that is conserved among species and implicated in various human diseases including leukemia, cardiovascular diseases, and metabolic disorders. However, the role of TRB1 in the immune response is not understood. To evaluate this role, we examined regulation of TRB1 expression and the function of TRB1 in interleukin-2 (IL-2) induction in Jurkat cells, a human acute T cell leukemia cell line. We found that TRB1 was strongly induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin in these cells. IL-2 expression was induced in Jurkat cells activated by PMA and ionomycin; however, knockdown of TRB1 resulted in decreased induction of IL-2. TRB1 null Jurkat cells established using the CRISPR/Cas9 system also showed reduction of IL-2 expression on PMA/ionomycin stimulation. TRB1 knockdown also markedly inhibited IL-2 promoter activation. To determine the mechanism of the stimulatory effect on IL-2 induction, we focused on histone deacetylases (HDACs), and found that HDAC1 preferentially interacts with TRB1. TRB1 suppressed the interaction of HDAC1 with nuclear factor of activated T cells 2 (NFAT2), which is a crucial transcription factor for IL-2 induction. These results indicate that TRB1 is a positive regulator of IL-2 induction in activated T cells.

  12. Absolute Side-chain Structure at Position 13 Is Required for the Inhibitory Activity of Bromein*

    PubMed Central

    Sawano, Yoriko; Hatano, Ken-ichi; Miyakawa, Takuya; Tanokura, Masaru

    2008-01-01

    Bromelain isoinhibitor (bromein), a cysteine proteinase inhibitor from pineapple stem, has a unique double-chain structure. The bromein precursor protein includes three homologous inhibitor domains, each containing an interchain peptide between the light and heavy chains. The interchain peptide in the single-chain precursor is immediately processed by bromelain, a target proteinase. In the present study, to clarify the essential inhibitory site of bromein, we constructed 44 kinds of site-directed and deletion mutants and investigated the inhibitory activity of each toward bromelain. As a result, the complete chemical structure of Leu13 in the light chain was revealed to be essential for inhibition. Pro12 prior to the leucine residue was also involved in the inhibitory activity and would control the location of the leucine side chain by the fixed φ dihedral angle of proline. Furthermore, the five-residue length of the interchain peptide was strictly required for the inhibitory activity. On the other hand, no inhibitory activity against bromelain was observed by the substitution of proline for the N terminus residue Thr15 of the interchain peptide. In summary, these mutational analyses of bromein demonstrated that the appropriate position and conformation of Leu13 are absolutely crucial for bromelain inhibition. PMID:18948264

  13. Positive association between physical activity and PER3 expression in older adults

    PubMed Central

    Takahashi, Masaki; Haraguchi, Atsushi; Tahara, Yu; Aoki, Natsumi; Fukazawa, Mayuko; Tanisawa, Kumpei; Ito, Tomoko; Nakaoka, Takashi; Higuchi, Mitsuru; Shibata, Shigenobu

    2017-01-01

    The circadian clock regulates many physiological functions including physical activity and feeding patterns. In addition, scheduled exercise and feeding themselves can affect the circadian clock. The purpose of the present study was to investigate the relationship between physical/feeding activity and expression of clock genes in hair follicle cells in older adults. Twenty adult men (age, 68 ± 7 years, mean ± SE) were examined in this cross-sectional study. Prior to hair follicle cell collection, the participants were asked to wear a uniaxial accelerometer for one week. The timings of breakfast, lunch, and dinner were also recorded. Hair follicle cells were then collected over a 24 h period at 4 h intervals. The amplitude of PER3 expression was positively correlated with moderate and vigorous physical activity (r = 0.582, p = 0.007) and peak oxygen uptake (r = 0.481, p = 0.032), but these correlations were not observed for NR1D1 or NR1D2. No association was noted between meal times and the amplitude or the acrophase for any of these three clock genes. These findings suggest that rhythmic expression of the circadian clock gene PER3 is associated with the amount of daily physical activity and physical fitness in older adults. PMID:28045078

  14. Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ

    PubMed Central

    Meyerson, Anna F.; Lessing, Juan N.; Itakura, Kaoru; Hylton, Nola M.; Wolverton, Dulcy E.; Joe, Bonnie N.; Esserman, Laura J.; Hwang, E. Shelley

    2014-01-01

    Introduction An option for active surveillance is not currently offered to patients with ductal carcinoma in situ (DCIS); however a small number of women decline standard surgical treatment for noninvasive cancer. The purpose of this study was to assess outcomes in a cohort of 14 well-informed women who elected non-surgical active surveillance with endocrine treatment alone for estrogen receptor-positive DCIS. Methods Retrospective review of 14 women, 12 of whom were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant endocrine therapy prior to definitive surgical management. The patients in this report withdrew from the parent study opting instead for active surveillance with endocrine treatment and imaging. Results 8 women had surgery at a median follow up of 28.3 months (range 10.1–70 months), 5 had stage I IDC at surgical excision, and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive disease for a median of 31.8 months (range 11.8–80.8 months). Conclusion Long-term active surveillance for DCIS is feasible in a well-informed patient population, but is associated with risk of invasive cancer at surgical excision. PMID:21843942

  15. Tribolium castaneum defensins are primarily active against Gram-positive bacteria.

    PubMed

    Tonk, Miray; Knorr, Eileen; Cabezas-Cruz, Alejandro; Valdés, James J; Kollewe, Christian; Vilcinskas, Andreas

    2015-11-01

    The red flour beetle Tribolium castaneum is a destructive insect pest of stored food and feed products, and a model organism for development, evolutionary biology and immunity. The insect innate immune system includes antimicrobial peptides (AMPs) with a wide spectrum of targets including viruses, bacteria, fungi and parasites. Defensins are an evolutionarily-conserved class of AMPs and a potential new source of antimicrobial agents. In this context, we report the antimicrobial activity, phylogenetic and structural properties of three T. castaneum defensins (Def1, Def2 and Def3) and their relevance in the immunity of T. castaneum against bacterial pathogens. All three recombinant defensins showed bactericidal activity against Micrococcus luteus and Bacillus thuringiensis serovar tolworthi, but only Def1 and Def2 showed a bacteriostatic effect against Staphylococcus epidermidis. None of the defensins showed activity against the Gram-negative bacteria Escherichia coli and Pseudomonas entomophila or against the yeast Saccharomyces cerevisiae. All three defensins were transcriptionally upregulated following a bacterial challenge, suggesting a key role in the immunity of T. castaneum against bacterial pathogens. Phylogenetic analysis showed that defensins from T. castaneum, mealworms, Udo longhorn beetle and houseflies cluster within a well-defined clade of insect defensins. We conclude that T. castaneum defensins are primarily active against Gram-positive bacteria and that other AMPs may play a more prominent role against Gram-negative species.

  16. Immunohistochemical quantitation of oestrogen receptors and proliferative activity in oestrogen receptor positive breast cancer.

    PubMed Central

    Jensen, V; Ladekarl, M

    1995-01-01

    AIM--To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content (oestrogen receptor index) and proliferative activity (MIB-1 index) in breast cancer. METHODS--Two monoclonal antibodies, MIB-1 and oestrogen receptor, were applied to formalin fixed, paraffin wax embedded tissue from 25 prospectively collected oestrogen receptor positive breast carcinomas, using a microwave antigen retrieval method. Tumour tissue was allocated systematically to different periods of fixation to ensure minimal intraspecimen variation. The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sampled systematically from the entire specimen and from the whole tumour area of one "representative" cross-section. RESULTS--No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation. The estimated MIB-1 and oestrogen receptor indices in tissue sampled systematically from the entire tumour were closely correlated with estimates obtained in a "representative" section. The intra- and interobserver correlation of the MIB-1 index was good, although a slight systematical error at the second assessment of the intraobserver study was noted. CONCLUSION--Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin, varying from less than four hours to more than 48 hours. The MIB-1 and the oestrogen receptor indices obtained in a "representative" section do not deviate significantly from average indices determined in tissue samples from the entire tumour. Finally, the estimation of MIB-1 index is reproducible, justifying its routine use. PMID:7629289

  17. 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.

  18. 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

    2015-12-08

    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.

  19. Combining global positioning system and accelerometer data to determine the locations of physical activity in children.

    PubMed

    Oreskovic, Nicolas M; Blossom, Jeff; Field, Alison E; Chiang, Sylvia R; Winickoff, Jonathan P; Kleinman, Ronald E

    2012-05-01

    National trends indicate that children and adolescents are not achieving sufficient levels of physical activity. Combining global positioning system (GPS) technology with accelerometers has the potential to provide an objective determination in locations where youth engage in physical activity. The aim of this study was to identify the optimal methods for collecting combined accelerometer and GPS data in youth, to best locate where children spend time and are physically active. A convenience sample of 24 mid-school children in Massachusetts was included. Accelerometers and GPS units were used to quantify and locate childhood physical activity over 5 weekdays and 2 weekend days. Accelerometer and GPS data were joined by time and mapped with a geographical information system (GIS) using ArcGIS software. Data were collected in winter, spring, summer in 2009-2010, collecting a total of 26,406 matched datapoints overall. Matched data yield was low (19.1% total), regardless of season (winter, 12.8%; spring, 30.1%; summer, 14.3%). Teacher-provided, pre-charged equipment yielded the most matched (30.1%; range: 10.1-52.3%) and greatest average days (6.1 days) of data. Across all seasons, children spent most of their time at home. Outdoor use patterns appeared to vary by season, with street use increasing in spring, and park and playground use increasing in summer. Children spent equal amounts of physical activity time at home and walking in the streets. Overall, the various methods for combining GPS and accelerometer data provided similarly low amounts of combined data. No combined GPS and accelerometer data collection method proved superior in every data return category, but use of GIS to map joined accelerometer and GPS data can demarcate childhood physical activity locations.

  20. 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.

  1. Automated time activity classification based on global positioning system (GPS) tracking data

    PubMed Central

    2011-01-01

    Background Air pollution epidemiological studies are increasingly using global positioning system (GPS) to collect time-location data because they offer continuous tracking, high temporal resolution, and minimum reporting burden for participants. However, substantial uncertainties in the processing and classifying of raw GPS data create challenges for reliably characterizing time activity patterns. We developed and evaluated models to classify people's major time activity patterns from continuous GPS tracking data. Methods We developed and evaluated two automated models to classify major time activity patterns (i.e., indoor, outdoor static, outdoor walking, and in-vehicle travel) based on GPS time activity data collected under free living conditions for 47 participants (N = 131 person-days) from the Harbor Communities Time Location Study (HCTLS) in 2008 and supplemental GPS data collected from three UC-Irvine research staff (N = 21 person-days) in 2010. Time activity patterns used for model development were manually classified by research staff using information from participant GPS recordings, activity logs, and follow-up interviews. We evaluated two models: (a) a rule-based model that developed user-defined rules based on time, speed, and spatial location, and (b) a random forest decision tree model. Results Indoor, outdoor static, outdoor walking and in-vehicle travel activities accounted for 82.7%, 6.1%, 3.2% and 7.2% of manually-classified time activities in the HCTLS dataset, respectively. The rule-based model classified indoor and in-vehicle travel periods reasonably well (Indoor: sensitivity > 91%, specificity > 80%, and precision > 96%; in-vehicle travel: sensitivity > 71%, specificity > 99%, and precision > 88%), but the performance was moderate for outdoor static and outdoor walking predictions. No striking differences in performance were observed between the rule-based and the random forest models. The random forest model was fast and easy to execute

  2. 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

  3. 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.

  4. 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

  5. Positive correlation between type 1 and 2 iodothyronine deiodinases activities in human goiters.

    PubMed

    Pereira, Valmara S; Marassi, Michelle P; Rosenthal, Doris; Vaisman, Mário; Corrêa da Costa, Vânia M

    2012-06-01

    Type 1 (D1) and 2 (D2) iodothyronine deiodinases are selenocysteine-containing enzymes that catalyze the deiodination of T4 to T3 in the thyroid and in peripheral tissues. Despite their importance to the plasma T3 pool in human beings, there are few studies about their behavior in human thyroids. In order to better understand iodothyronine deiodinase regulation in the thyroid gland, we studied thyroid tissue samples from follicular adenoma (AD, n = 5), toxic diffuse goiter (TDG, n = 6), nontoxic multinodular goiter (NMG, n = 40), papillary thyroid carcinoma (PTC, n = 8), and surrounding normal tissues (NT, n = 7) from 36 patients submitted to elective thyroidectomy. D1 and D2 activities were determined by quantification of the radioiodine released by ¹²⁵I-rT3 or ¹²⁵I-T4 under standardized conditions, and expressed as pmol rT3 deiodinated per minute and mg protein (pmol rT3 min⁻¹ mg⁻¹ ptn) and fmol T4 deiodinated per minute and mg protein (fmol T4 min⁻¹ mg⁻¹ ptn), respectively. D1 activity detected in TDG and AD tissues were significantly higher than in NT, PTC or NMG samples. D2 activity was also significantly higher in TDG and AD samples than in PTC, NMG, or NT. There was great variability in D1 and D2 enzymatic activities from distinct patients as well as from different areas from the same goiter. There was a positive correlation (P < 0,0001, r = 0.4942) between D1 and D2 activities when all samples were taken into account, suggesting that-in the thyroid-these two iodothyronine deiodinases may have related regulatory mechanisms, even if conditioned by other as yet unknown factors.

  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.

  7. Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene.

    PubMed

    Lefebure, Marcus; Tothill, Richard W; Kruse, Elizabeth; Hawkins, Edwin D; Shortt, Jake; Matthews, Geoffrey M; Gregory, Gareth P; Martin, Benjamin P; Kelly, Madison J; Todorovski, Izabela; Doyle, Maria A; Lupat, Richard; Li, Jason; Schroeder, Jan; Wall, Meaghan; Craig, Stuart; Poortinga, Gretchen; Cameron, Don; Bywater, Megan; Kats, Lev; Gearhart, Micah D; Bardwell, Vivian J; Dickins, Ross A; Hannan, Ross D; Papenfuss, Anthony T; Johnstone, Ricky W

    2017-03-06

    The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.

  8. Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

    PubMed Central

    Lefebure, Marcus; Tothill, Richard W.; Kruse, Elizabeth; Hawkins, Edwin D.; Shortt, Jake; Matthews, Geoffrey M.; Gregory, Gareth P.; Martin, Benjamin P.; Kelly, Madison J.; Todorovski, Izabela; Doyle, Maria A.; Lupat, Richard; Li, Jason; Schroeder, Jan; Wall, Meaghan; Craig, Stuart; Poortinga, Gretchen; Cameron, Don; Bywater, Megan; Kats, Lev; Gearhart, Micah D.; Bardwell, Vivian J.; Dickins, Ross A.; Hannan, Ross D.; Papenfuss, Anthony T.; Johnstone, Ricky W.

    2017-01-01

    The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis. PMID:28262675

  9. 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

  10. Change in sexual activity 12 months after ART initiation among HIV-positive Mozambicans.

    PubMed

    Pearson, Cynthia R; Cassels, Susan; Kurth, Ann E; Montoya, Pablo; Micek, Mark A; Gloyd, Stephen S

    2011-05-01

    We assessed sexual behaviors before and 12-months after ART initiation among 277 Mozambicans attending an HIV clinic. Measured behaviors included the number of sexual partners, condom use, concurrent relationships, disclosure of HIV status, alcohol use, and partners' serostatus. Compared to before ART initiation, increases were seen 12 months after ART in the proportion of participants who were sexually active (48% vs. 64% respondents, P < 0.001) and the proportion of participants with HIV-negative or unknown serostatus partners (45% vs. 80%, P < 0.001). Almost all (96%) concurrent partnerships reported at 12 months formed after ART initiation. Although reported correct and consist condom use increased, the number of unprotected sexual relationships remained the same (n = 45). Non-disclosure of HIV-serostatus to sexual partners was the only significant predictor of practicing unprotected sex with partners of HIV-negative or unknown serostatus. Sexual activity among HIV-positive persons on ART increased 12 months after ART initiation. Ongoing secondary transmission prevention programs addressing sexual activity with multiple partners, disclosure to partners and consistent condom use with serodisconcordant partners must be incorporated throughout HIV care programs.

  11. Positive and negative regulation of T-cell activation through kinases and phosphatases.

    PubMed Central

    Mustelin, Tomas; Taskén, Kjetil

    2003-01-01

    The sequence of events in T-cell antigen receptor (TCR) signalling leading to T-cell activation involves regulation of a number of protein tyrosine kinases (PTKs) and the phosphorylation status of many of their substrates. Proximal signalling pathways involve PTKs of the Src, Syk, Csk and Tec families, adapter proteins and effector enzymes in a highly organized tyrosine-phosphorylation cascade. In intact cells, tyrosine phosphorylation is rapidly reversible and generally of a very low stoichiometry even under induced conditions due to the fact that the enzymes removing phosphate from tyrosine-phosphorylated substrates, the protein tyrosine phosphatases (PTPases), have a capacity that is several orders of magnitude higher than that of the PTKs. It follows that a relatively minor change in the PTK/PTPase balance can have a major impact on net tyrosine phosphorylation and thereby on activation and proliferation of T-cells. This review focuses on the involvement of PTKs and PTPases in positive and negative regulation of T-cell activation, the emerging theme of reciprocal regulation of each type of enzyme by the other, as well as regulation of phosphotyrosine turnover by Ser/Thr phosphorylation and regulation of localization of signal components. PMID:12485116

  12. Change in Sexual Activity 12 Months After ART Initiation Among HIV-Positive Mozambicans

    PubMed Central

    Cassels, Susan; Kurth, Ann E.; Montoya, Pablo; Micek, Mark A.; Gloyd, Stephen S.

    2012-01-01

    We assessed sexual behaviors before and 12-months after ART initiation among 277 Mozambicans attending an HIV clinic. Measured behaviors included the number of sexual partners, condom use, concurrent relationships, disclosure of HIV status, alcohol use, and partners’ serostatus. Compared to before ART initiation, increases were seen 12 months after ART in the proportion of participants who were sexually active (48% vs. 64% respondents, P < 0.001) and the proportion of participants with HIV-negative or unknown serostatus partners (45% vs. 80%, P < 0.001). Almost all (96%) concurrent partnerships reported at 12 months formed after ART initiation. Although reported correct and consist condom use increased, the number of unprotected sexual relationships remained the same (n = 45). Non-disclosure of HIV-serostatus to sexual partners was the only significant predictor of practicing unprotected sex with partners of HIV-negative or unknown serostatus. Sexual activity among HIV-positive persons on ART increased 12 months after ART initiation. Ongoing secondary transmission prevention programs addressing sexual activity with multiple partners, disclosure to partners and consistent condom use with serodisconcordant partners must be incorporated throughout HIV care programs. PMID:21082338

  13. Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation.

    PubMed

    Datko, Michael; Pineda, Jaime A; Müller, Ralph-Axel

    2017-02-28

    Autism has been characterized by atypical task-related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience-dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self-regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu-rhythm-based NFT in children with high-functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8-17). During an functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre- vs. post-training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu-rhythm NFT may be beneficial to individuals with ASD.

  14. 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.

  15. Antibacterial activity of oregano (Origanum vulgare Linn.) against gram positive bacteria.

    PubMed

    Saeed, Sabahat; Tariq, Perween

    2009-10-01

    The present investigation is focused on antibacterial potential of infusion, decoction and essential oil of oregano (Origanum vulgare) against 111 Gram-positive bacterial isolates belonging to 23 different species related to 3 genera. Infusion and essential oil exhibited antibacterial activity against Staphylococcus saprophyticus, S. aureus, Micrococcus roseus, M. kristinae, M. nishinomiyaensis, M. lylae, M. luteus, M. sedentarius, M. varians, Bacillus megaterium, B. thuringiensis, B. alvei, B. circulans, B. brevis, B. coagulans, B. pumilus, B. laterosporus, B. polymyxa, B. macerans, B. subtilis, B. firmus, B. cereus and B. lichiniformis. The infusion exhibited maximum activity against B. laterosporus (17.5 mm mean zone of inhibition+/-1.5 Standard deviation) followed by B. polymyxa (17.0 mm+/-2.0 SD) and essential oil of oregano exhibited maximum activity against S. saprophyticus (16.8 mm+/-1.8 SD) followed by B. circulans (14.5 mm+/-0.5 SD). While all these tested isolates were found resistant to decoction of oregano.

  16. Graminicide insensitivity correlates with herbicide-binding co-operativity on acetyl-CoA carboxylase isoforms.

    PubMed

    Price, Lindsey J; Herbert, Derek; Moss, Stephen R; Cole, David J; Harwood, John L

    2003-10-15

    The sensitivity of grass species to important classes of graminicide herbicides inhibiting ACCase (acetyl-CoA carboxylase) is associated with a specific inhibition of the multifunctional ACCase located in the plastids of grasses. In contrast, the multisubunit form of ACCase found in the chloroplasts of dicotyledonous plants is insensitive and the minor cytosolic multifunctional isoforms of the enzyme in both types of plants are also less sensitive to inhibition. We have isolated, separated and characterized the multifunctional ACCase isoforms found in exceptional examples of grasses that are either inherently insensitive to these graminicides, or from biotypes showing acquired resistance to their use. Major and minor multifunctional enzymes were isolated from cell suspension cultures of Festuca rubra and the 'Notts A1'-resistant biotype of Alopecurus myosuroides, and their properties compared with those isolated from cells of wild-type sensitive A. myosuroides or from sensitive maize. Purifications of up to 300-fold were necessary to separate the two isoforms. The molecular masses (200-230 kDa) and K(m) values for all three substrates (ATP, bicarbonate and acetyl-CoA) were similar for the different ACCases, irrespective of their graminicide sensitivity. Moreover, we found no correlation between the ability of isoforms to carboxylate propionyl-CoA and their sensitivity to graminicides. However, insensitive purified forms of ACCase were characterized by herbicide-binding co-operativity, whereas, in contrast, sensitive forms of the enzymes were not. Our studies on isolated individual isoforms of ACCase from grasses support and extend previous indications that herbicide binding co-operativity is the only kinetic property that differentiates naturally or selected insensitive enzymes from the typical sensitive forms usually found in grasses.

  17. CXCL8/IL-8 and CXCL12/SDF-1α Co-operatively Promote Invasiveness and Angiogenesis in Pancreatic Cancer

    PubMed Central

    Matsuo, Yoichi; Ochi, Nobuo; Sawai, Hirozumi; Yasuda, Akira; Takahashi, Hiroki; Funahashi, Hitoshi; Takeyama, Hiromitsu; Tong, Zhimin; Guha, Sushovan

    2009-01-01

    CXC-chemokines are involved in the chemotaxis of neutrophils, lymphocytes and monocytes. However, role of these chemokines in tumorigenesis, especially with regard to interaction between tumor and its microenvironment, has not been clearly elucidated. The purpose of this study was to analyze the co-operative role of CXCL8 and CXCL12 in the tumor-stromal interaction in pancreatic cancer (PaCa). Using ELISA and RT-PCR, we initially confirmed the expression of ligands and receptors, respectively, of CXC-chemokines in PaCa and stromal cells. We examined the co-operative role of CXCL8 and CXCL12 in proliferation/invasion of PaCa and human umbilical vein endothelial cells (HUVECs), and in HUVEC tube-formations through tumor-stromal interaction by MTS, Matrigel invasion, and angiogenesis assays, respectively. We detected expression of CXCR4, but not CXCR2, in all PaCa cells and fibroblasts. PaCa cells secreted CXCL8, and fibroblast cells secreted CXCL12. CXCL8 production in PaCa was significantly enhanced by CXCL12, and CXCL12 production in fibroblasts was significantly enhanced by co-culturing with PaCa. CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. CXCL12 enhanced the proliferation/invasion of HUVECs and the invasion of PaCa cells but had no effect on tube formation of HUVEC. We showed that PaCa-derived CXCL8 and fibroblast-derived CXCL12 cooperatively induced angiogenesis in vitro by promoting HUVEC proliferation, invasion, and tube formation. Thus, corresponding receptors CXCR2 and CXCR4 are potential antiangiogenic and antimetastatic therapeutic targets in PaCa. PMID:19035451

  18. A virtual intranet and data-warehousing for healthcare co-operation.

    PubMed

    Kerkri, E M; Quantin, C; Grison, T; Allaert, F A; Tchounikine, A; Yétongnon, K

    2001-01-01

    As patient's medical data is disseminated in different health structures, developing a medical or epidemiological patient-oriented data warehouse has some specific requirements compared to intra healthcare structure data-warehousing projects. The difference is that the healthcare structures implicated in a patient-oriented data warehouse project require some considerations about the confidentiality of the patient data and of the activities of healthcare structures. Building a data-warehousing system at a regional level, for example in cancerology, requires the participation of all concerned health structures, as well as different health professionals. The heterogeneity of sources medical data of has to be taken into account for choosing between several organizational configurations of the data warehousing system. In top of data warehousing, we propose a concept of Virtual Intranet, which provides a solution to the problem of medical information security arising from heterogeneous sources.

  19. Emerging and existing mechanisms co-operate in generating diverse β-lactam resistance phenotypes in geographically dispersed and genetically disparate Pseudomonas aeruginosa strains.

    PubMed

    Martinez, Elena; Pérez, Javier Escobar; Márquez, Carolina; Vilacoba, Elisabet; Centrón, Daniela; Leal, Aura L; Saavedra, Carlos; Saavedra, Sandra Y; Tovar, Catalina; Vanegas, Natasha; Stokes, H W

    2013-09-01

    β-Lactam resistance in Pseudomonas aeruginosa clinical isolates is driven by a number of mechanisms. Whilst several are understood, how they act co-operatively in pathogenic strains is less clear. In some isolates, resistance profiles cannot always be explained by identifying the common resistance-determining pathways, suggesting that other mechanisms may be important. Pathogenic P. aeruginosa isolates from four countries were characterised by PCR. Quantitative expression analysis was also assessed for the activity of several pathways that influence antibiotic resistance, and culture experiments were conducted to test how random transposition of the insertion sequence IS26 during growth may influence resistance to some antibiotics. In most strains, antibiotic resistance was being driven by changes in multiple pathways and by the presence or absence of genes acquired by lateral gene transfer. Multiple mechanisms of resistance were prevalent in strains from all of the countries examined, although regional differences in the type of interacting mechanisms were apparent. Changes in chromosomal pathways included overexpression of AmpC and two efflux pumps. Also, gain or loss of IS26 at some chromosomal locations, most notably oprD, could influence resistance to carbapenems. IS26-related resistance was found in strains from Argentina and geographically linked Uruguay, but not in strains from either Colombia or Australia. Pseudomonas aeruginosa pathogenic strains are evolving to become multidrug-resistant in more complex ways. This is being influenced by single strains acquiring changes in numerous known pathways as well as by newly emerging resistance mechanisms in this species.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Antibacterial activity of Withania somnifera against Gram-positive isolates from pus samples

    PubMed Central

    Bisht, Punum; Rawat, Vinita

    2014-01-01

    Background: Withania somnifera is an important medicinal plant that has been used in Ayurvedic and indigenous medicine since ancient times. In the view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. Attention has been drawn to antibacterial activity of the plant and its metabolites due to the challenge on growing antibacterial resistant pathogens. Aim: To examine the antimicrobial potential of leaf extract of W. somnifera against Gram-positive cocci. Materials and Methods: In this study, leaf extract of W. somnifera was used to examine their antimicrobial potential against Gram-positive cocci (n = 20) from pus samples of patients admitted in Government Medical College, Haldwani. Agar well diffusion method was used by taking methanolic leaf extract of W. somnifera. Results: It was observed that the methanolic leaf extract of W. somnifera was very effective in inhibiting the test pathogens including methicillin resistant Staphylococcus aureus and Enterococcus spp., with an average zone of inhibition of 20.6 mm and 19.4 mm at 2 mg/ml (100 μl) concentration, respectively. Conclusion: These results indicate that the antimicrobial property of W. somnifera leaf supports the traditional use of the plant in therapeutic use against microbial infections. PMID:25972723

  7. Using the Global Positioning System to monitor dynamic ground deformation networks on potentially active landslides

    NASA Astrophysics Data System (ADS)

    Moss, Jane L.

    The Global Positioning System (GPS) has many advantages over conventional surveying for landslide disaster prevention and mitigation. Once an initial baseline network of ground markers has been positioned, the re-occupation of survey stations determines ground deformation. This verifies both the boundary of the landslide block and ground surface changes. These changes may take the form of either slow to moderate creep, or massive structural failure. Creep may occur as a precursor to slope failure, either within (i) fresh slopes that do not show any evidence of past collapse, (ii) the existing active landslides and (iii) areas adjacent to existing collapses. Networks are measured using rapid static GPS. The method, which enables many survey stations to be measured in a short time, provides a quick means for determining the three-dimensional map of the ground surface (of the landslide). A study in Gran Canaria, Canary Islands, established an initial baseline network within the Barranco de Tirajana, a basin on Gran Canaria that contains evidence of both ancient and recent landslides. Reoccupation of the network using rapid static GPS revealed a field accuracy of approximately 10 mm; the data indicated that the most recent landslide is currently stable.

  8. 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

  9. Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis.

    PubMed

    Davis, G L; Czaja, A J; Taswell, H F; Ludwig, J; Go, V L

    1985-02-01

    To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HBcAg was evaluated in 16 patients with severe HBsAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean +/- SEM, 66 +/- 9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HBcAg and in liver tissue by indirect immunoperoxidase staining for HBcAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HBcAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HBcAg appeared in only one patient in whom no virus replication was detected prior to therapy. HBeAg was frequently detected at low titers by radioimmunoassay when serum HBcAg was undetectable. Loss of HBcAg preceded loss of HBeAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HBcAg; in three of these, disease activity continued after loss of HBeAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HBeAg and absence of detectable virus replication.

  10. 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

  11. Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana

    PubMed Central

    Lawler, Kathy; Jeremiah, Kealeboga; Mosepele, Mosepele; Ratcliffe, Sarah J.; Cherry, Catherine; Seloilwe, Esther; Steenhoff, Andrew P.

    2011-01-01

    Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment. PMID:21365002

  12. 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

  13. LYN-activating mutations mediate antiestrogen resistance in estrogen receptor–positive breast cancer

    PubMed Central

    Schwarz, Luis J.; Fox, Emily M.; Balko, Justin M.; Garrett, Joan T.; Kuba, María Gabriela; Estrada, Mónica Valeria; González-Angulo, Ana María; Mills, Gordon B.; Red-Brewer, Monica; Mayer, Ingrid A.; Abramson, Vandana; Rizzo, Monica; Kelley, Mark C.; Meszoely, Ingrid M.; Arteaga, Carlos L.

    2014-01-01

    Estrogen receptor–positive (ER+) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER+ tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER+ breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER+ LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYND189Y has higher catalytic activity than WT protein. Further, LYND189Y exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYNWT. Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYND189Y overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER+ breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER+ xenografts but not LYND189Y-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER+ breast cancers. PMID:25401474

  14. Gram-positive bacterial cell envelopes: The impact on the activity of antimicrobial peptides.

    PubMed

    Malanovic, Nermina; Lohner, Karl

    2016-05-01

    A number of cationic antimicrobial peptides, effectors of innate immunity, are supposed to act at the cytoplasmic membrane leading to permeabilization and eventually membrane disruption. Thereby, interaction of antimicrobial peptides with anionic membrane phospholipids is considered to be a key factor in killing of bacteria. Recently, evidence was provided that killing takes place only when bacterial cell membranes are completely saturated with peptides. This adds to an ongoing debate, which role cell wall components such as peptidoglycan, lipoteichoic acid and lipopolysaccharide may play in the killing event, i.e. if they rather entrap or facilitate antimicrobial peptides access to the cytoplasmic membrane. Therefore, in this review we focused on the impact of Gram-positive cell wall components for the mode of action and activity of antimicrobial peptides as well as in innate immunity. This led us to conclude that interaction of antimicrobial peptides with peptidoglycan may not contribute to a reduction of their antimicrobial activity, whereas interaction with anionic lipoteichoic acids may reduce the local concentration of antimicrobial peptides on the cytoplasmic membrane necessary for sufficient destabilization of the membranes and bacterial killing. Further affinity studies of antimicrobial peptides toward the different cell wall as well as membrane components will be needed to address this problem on a quantitative level. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.

  15. From Docking False-Positive to Active Anti-HIV Agent

    PubMed Central

    Barreiro, Gabriela; Kim, Joseph T.; Guimarães, Cristiano R. W.; Bailey, Christopher M.; Domaoal, Robert A.; Wang, Ligong; Anderson, Karen S.

    2008-01-01

    Virtual screening of the Maybridge library of ca. 70,000 compounds was performed using a similarity filter, docking, and MM-GB/SA post-processing to seek potential non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Though known NNRTIs were retrieved well, purchase and assaying of representative, top-scoring compounds from the library failed to yield any active anti-HIV agents. However, the highest-ranked library compound, oxadiazole 1, was pursued as a potential “near-miss” with the BOMB program to seek constructive modifications. Subsequent synthesis and assaying of several polychloro-analogs did yield anti-HIV agents with EC50 values as low as 310 nM. The study demonstrates that it is possible to learn from a formally unsuccessful virtual-screening exercise and, with the aid of computational analyses, to evolve efficiently a false positive into a true active. In addition, the need for adequate structure validation was confirmed by the apparent misrepresentation of a purchased compound elsewhere as the present oxadiazole core compound, 16. PMID:17918923

  16. Relationship between lower limb position and pelvic floor muscle surface electromyography activity in menopausal women: a prospective observational study

    PubMed Central

    Halski, Tomasz; Ptaszkowski, Kuba; Słupska, Lucyna; Dymarek, Robert; Paprocka-Borowicz, Małgorzata

    2017-01-01

    Objectives In physiotherapeutic practice, special attention is being given to the reciprocal anatomical, physiological, and biomechanical relationship of the pelvis and the structures connected to it. However, the scientific literature shows mainly the theoretical information about their mutual connections. The lack of information about these relations from a practical aspect coupled with the paucity of scientific papers on the impact of posture changes on the pelvic floor led the authors to conduct this study. The primary aim of this study was to compare the resting and functional bioelectrical activities of pelvic floor muscles (PFMs) depending on three different positions of the lower limbs (positions A, B, and C) in the supine position. Materials and methods This was a prospective observational study evaluating resting and functional activities of the PFM depending on the position of the lower limbs. The study was carried out at the Department and Clinic of Urology, University Hospital in Wroclaw, Poland and the target group were women in the menopausal period. Bioelectrical activity of PFM was recorded using a surface electromyographic instrument in the supine position. Results of the values obtained in A, B, and C positions were compared using a one-way analysis of variance. Results In position A, the average resting surface electromyography (sEMG) activity of PFM was 6.9±2.6 µV; in position B, the result was 6.9±2.5 µV and in position C, the resting sEMG activity was 5.7±1.8 µV (P=0.0102). The results of the functional bioelectrical activity of PFM were as follows: position A – 20.3±11.8 µV, position B – 19.9±10.6 µV, and position C – 25.3±10.9 µV (P=0.0104). Conclusion The results showed that in the supine position, the PFM achieved the lowest resting activity and the highest functional activity. Therefore, the supine position can be recommended for the diagnosis and therapy of weakened PFM. PMID:28115836

  17. In-vitro activities of 14-, 15- and 16-membered macrolides against gram-positive cocci.

    PubMed

    Hamilton-Miller, J M

    1992-02-01

    The in-vitro activities of the 14-membered macrolides erythromycin, dirithromycin, roxithromycin, clarithromycin, the 15-membered compound azithromycin and the 16-membered macrolides (16 MM) josamycin, spiramycin and midecamycin acetate (MOM) have been compared against staphylococci, enterococci and streptococci. Results have been analysed separately according to the sensitivity status of the tested strains to erythromycin, namely sensitive (S), inducibly resistant (IR) or constitutively resistant (CR). 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin. The 16 MM were slightly less active against S strains than were the 14- and 15-membered compounds, and inhibited most IR strains; MOM and josamycin were about twice as potent as spiramycin. IR and S Staphylococcus aureus strains were equally sensitive to 16 MM, while IR strains of coagulase-negative staphylococci were less sensitive than were S strains. All CR strains of S. aureus were resistant to 16 MM, as were most of the other CR strains. However, 5/21 CR coagulase-negative staphylococci and 2/20 CR enterococci tested were sensitive to 16 MM. The seven CR strains showing anomalous sensitivity to the 16 MM (five Staphylococcus haemolyticus and two enterococci) were only 'moderately resistant' to erythromycin (MIC 8-64 mg/L), while all the other CR strains were 'highly resistant' (MIC greater than 128 mg/L). These results indicate that it may be difficult to predict the sensitivity of Gram-positive cocci to 16 MM, and therefore individual sensitivity testing to specific compounds is essential.

  18. 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

  19. Associations among central nervous, endocrine, and immune activities when positive emotions are elicited by looking at a favorite person.

    PubMed

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

    2008-03-01

    Recent studies on psychoneuroimmunology have indicated that positive psychological events are related to immune functions; however, limited information is available regarding associations among the central nervous, endocrine, and immune systems when positive emotions are elicited. In the present study, we demonstrated associations among these systems by simultaneously recording brain, endocrine, and immune activities when positive emotions were evoked in participants as they watched films featuring their favorite persons. Interestingly, the activity of peripheral circulating natural killer cells and the peripheral dopamine level were elevated while participants experienced positive emotions, and these values were positively correlated. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, hypothalamus, subcallosal gyrus, posterior cingulate cortex, superior temporal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with endocrine and immune activities. These results suggest that while an individual experiences positive emotions, the central nervous, endocrine, and immune systems may be interrelated and attraction for favorite persons may be associated with the activation of the innate immune function via the dopaminergic system.

  20. Ankle Instability Effects on Joint Position Sense When Stepping Across the Active Movement Extent Discrimination Apparatus

    PubMed Central

    Witchalls, Jeremy; Waddington, Gordon; Blanch, Peter; Adams, Roger

    2012-01-01

    Context Individuals with and without functional ankle instability have been tested for deficits in lower limb proprioception with varied results. Objective To determine whether a new protocol for testing participants' joint position sense during stepping is reliable and can detect differences between participants with unstable and stable ankles. Design Descriptive laboratory study. Setting University clinical laboratory. Patients or Other Participants Sample of convenience involving 21 young adult university students and staff. Ankle stability was categorized by score on the Cumberland Ankle Instability Tool; 13 had functional ankle instability, 8 had healthy ankles. Intervention(s) Test-retest of ankle joint position sense when stepping onto and across the Active Movement Extent Discrimination Apparatus twice, separated by an interim test, standing still on the apparatus and moving only 1 ankle into inversion. Main Outcome Measure(s) Difference in scores between groups with stable and unstable ankles and between test repeats. Results Participants with unstable ankles were worse at differentiating between inversion angles underfoot in both testing protocols. On repeated testing with the stepping protocol, performance of the group with unstable ankles was improved (Cohen d = 1.06, P = .006), whereas scores in the stable ankle group did not change in the second test (Cohen d = 0.04, P = .899). Despite this improvement, the unstable group remained worse at differentiating inversion angles on the stepping retest (Cohen d = 0.99, P = .020). Conclusions The deficits on proprioceptive tests shown by individuals with functional ankle instability improved with repeated exposure to the test situation. The learning effect may be the result of systematic exposure to ankle-angle variation that led to movement-specific learning or increased confidence when stepping across the apparatus. PMID:23182010

  1. The Mid-Latitude Positive Bay and the MPB Index of Substorm Activity

    NASA Astrophysics Data System (ADS)

    McPherron, Robert L.; Chu, Xiangning

    2016-11-01

    Substorms are a major source of magnetic activity. At substorm expansion phase onset a westward current flows through the expanding aurora. This current is the ionospheric closure of the substorm current wedge produced by diversion of tail current along magnetic field lines. At low latitudes the field-aligned currents create a systematic pattern in the north (X) and east (Y) components of the surface magnetic field. The rise and decay in X is called a midlatitude positive bay whose start is a proxy for expansion onset. In this paper we describe a new index called the midlatitude positive bay index (MPB) which monitors the power in the substorm perturbations of X and Y. The index is obtained by removing the main field, storm time variations, and the solar quiet (Sq) variation from the measured field. These are estimated with spline fits and principal component analysis. The residuals of X and Y are high pass filtered to eliminate variations with period longer than 3 hours. The sum of squares of the X and Y power is determined at each of 35 midlatitude stations. The average power in night time stations is the MPB index. The index series is standardized and intervals above a fixed threshold are taken as possible bay signatures. Post processing constrains these to have reasonable values of rise time, strength, and duration. Minima in the index before and after the peak are taken as the start and end of the bay. The MPB and AL indices can be used to identify quiet intervals in the magnetic field.

  2. 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.

  3. cVEMP morphology changes with recording electrode position, but single motor unit activity remains constant.

    PubMed

    Rosengren, Sally M; Colebatch, James G; Borire, Adeniyi; Straumann, Dominik; Weber, Konrad P

    2016-04-15

    Cervical vestibular evoked myogenic potentials (cVEMPs) recorded over the lower quarter of the sternocleidomastoid (SCM) muscle in normal subjects may have opposite polarity to those recorded over the midpoint. It has thus been suggested that vestibular projections to the lower part of SCM might be excitatory rather than inhibitory. We tested the hypothesis that the SCM muscle receives both inhibitory and excitatory vestibular inputs. We recorded cVEMPs in 10 normal subjects with surface electrodes placed at multiple sites along the anterior (sternal) component of the SCM muscle. We compared several reference sites: sternum, ipsilateral and contralateral earlobes, and contralateral wrist. In five subjects, single motor unit responses were recorded at the upper, middle, and lower parts of the SCM muscle using concentric needle electrodes. The surface cVEMP had the typical positive-negative polarity at the midpoint of the SCM muscle. In all subjects, as the recording electrode was moved toward each insertion point, p13 amplitude became smaller and p13 latency increased, then the polarity inverted to a negative-positive waveform (n1-p1). Changing the reference site did not affect reflex polarity. There was a significant short-latency change in activity in 61/63 single motor units, and in each case this was a decrease or gap in firing, indicating an inhibitory reflex. Single motor unit recordings showed that the reflex was inhibitory along the entire SCM muscle. The cVEMP surface waveform inversion near the mastoid and sternal insertion points likely reflects volume conduction of the potential occurring with increasing distance from the motor point.

  4. The Mid-Latitude Positive Bay and the MPB Index of Substorm Activity

    NASA Astrophysics Data System (ADS)

    McPherron, Robert L.; Chu, Xiangning

    2017-03-01

    Substorms are a major source of magnetic activity. At substorm expansion phase onset a westward current flows through the expanding aurora. This current is the ionospheric closure of the substorm current wedge produced by diversion of tail current along magnetic field lines. At low latitudes the field-aligned currents create a systematic pattern in the north (X) and east (Y) components of the surface magnetic field. The rise and decay in X is called a midlatitude positive bay whose start is a proxy for expansion onset. In this paper we describe a new index called the midlatitude positive bay index (MPB) which monitors the power in the substorm perturbations of X and Y. The index is obtained by removing the main field, storm time variations, and the solar quiet (Sq) variation from the measured field. These are estimated with spline fits and principal component analysis. The residuals of X and Y are high pass filtered to eliminate variations with period longer than 3 hours. The sum of squares of the X and Y power is determined at each of 35 midlatitude stations. The average power in night time stations is the MPB index. The index series is standardized and intervals above a fixed threshold are taken as possible bay signatures. Post processing constrains these to have reasonable values of rise time, strength, and duration. Minima in the index before and after the peak are taken as the start and end of the bay. The MPB and AL indices can be used to identify quiet intervals in the magnetic field.

  5. 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.

  6. The immediate effect of changing mandibular position on the EMG activity of the masseter, temporalis, sternocleidomastoid, and trapezius muscles.

    PubMed

    Ceneviz, Caroline; Mehta, Noshir R; Forgione, Albert; Sands, M J; Abdallah, Emad F; Lobo Lobo, Silvia; Mavroudi, Sofia

    2006-10-01

    This study investigated the immediate effect of changing mandibular position on the electromyographic (EMG) activity of the masseter (MS), temporalis (TM), sternocleidomastoid (SCM) and trapezius (TR) muscles. Thirty-three (33) asymptomatic subjects (16 males and 17 females), ages 23 to 52 were selected. Surface EMG recordings were obtained for all muscles bilaterally with the mandible in a relaxed open position (relaxed) and during maximal voluntary clenching (fullbite) for the following: a non-repositioning appliance (NONREPOS) and repositioning appliance (REPOS). REPOS significantly reduced EMG activity of all muscles bilaterally during fullbite. During relaxation, reduction in EMG activity was only found for TR bilaterally. NONREPOS decreased the EMG activity bilaterally for TM and TR and unilaterally (left) for MS and SCM during fullbite. During relaxation, NONREPOS decreased muscle activity bilaterally for TR and SCM. A unilateral reduction was found for TM (right). These findings suggest that immediate alterations in mandibular position affect the cranio-cervical system. Both mandibular positions tested lowered the EMG activity of masticatory and cervical muscles in the relaxed and fullbite positions. The trapezius muscle was the most responsive to alterations in mandibular position.

  7. 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.

  8. [Improving team-oriented co-operation between physicians and nursing staff--opening new opportunities with process orientation and extended nursing roles].

    PubMed

    Dahlgaard, Knut

    2010-01-01

    Co-ordination in terms of synergetic co-operation of the two professional groups is highly demanding and requires creative measures. Co-operation between doctors and nurses can be improved by an integrative organisational concept agreed-upon by the parties involved. The core elements of this KoPM model include jointly practised patient orientation, a process organisation approach to health care provision, successful communication as well as a process support framework. Another task that needs to be performed will be to refine this approach by improving communication efficiency, by employing qualification processes and by evaluating cooperation projects.

  9. 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

  10. Use of global positioning system for physical activity research in youth: ESPAÇOS Adolescentes, Brazil.

    PubMed

    Alberico, Claudia Oliveira; Schipperijn, Jasper; Reis, Rodrigo S

    2016-12-23

    The built environment is an important factor associated with physical activity and sedentary behavior (SB) during adolescence. This study presents the methods for objective assessment of context-specific moderate to vigorous physical activity (MVPA) and SB, as well as describes results from the first project using such methodology in adolescents from a developing country. An initial sample of 381 adolescents was recruited from 32 census tracts in Curitiba, Brazil (2013); 80 had their homes geocoded and wore accelerometer and GPS devices for seven days. Four domains were defined as important contexts: home, school, transport and leisure. The majority of participants (n=80) were boys (46; 57.5%), with a normal BMI (52; 65.0%) and a mean age (SD) of 14.5 (5.5) years. Adolescents spent most of their time at home, engaging in SB. Overall, the largest proportion of MVPA was while in transport (17.1% of time spent in this context) and SB while in leisure (188.6min per day). Participants engaged in MVPA for a median of 28.7 (IQR 18.2-43.2) and 17.9 (IQR 9.2-32.1) minutes during week and weekend days, respectively. Participants spent most of their day in the leisure and home domains. The use of Geographic Information System (GIS), Global Positioning System (GPS) and accelerometer data allowed objective identification of the amount of time spent in MVPA and SB in four different domains. Though the combination of objective measures is still an emerging methodology, this is a promising and feasible approach to understanding interactions between people and their environments in developing countries.

  11. LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer.

    PubMed

    Schwarz, Luis J; Fox, Emily M; Balko, Justin M; Garrett, Joan T; Kuba, María Gabriela; Estrada, Mónica Valeria; González-Angulo, Ana María; Mills, Gordon B; Red-Brewer, Monica; Mayer, Ingrid A; Abramson, Vandana; Rizzo, Monica; Kelley, Mark C; Meszoely, Ingrid M; Arteaga, Carlos L

    2014-12-01

    Estrogen receptor-positive (ER(+)) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER(+) tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER(+) breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER(+) LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYN(D189Y) has higher catalytic activity than WT protein. Further, LYN(D189Y) exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYN(WT). Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYN(D189Y) overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER(+) breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER(+) xenografts but not LYN(D189Y)-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER(+) breast cancers.

  12. Positive anti‐cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis

    PubMed Central

    Elkayam, O; Segal, R; Lidgi, M; Caspi, D

    2006-01-01

    Objectives To determine the prevalence of anti‐cyclic citrullinated proteins (anti‐CCP) and IgM rheumatoid factor (RF) in sera of patients with TB compared with healthy controls. Patients and methods 47 consecutive patients with recently diagnosed active pulmonary TB and 39 healthy controls were studied. Data were collected by questionnaire on clinical features of the disease, duration of symptoms, fever, cough, arthralgia, myalgia, sicca symptoms. Serum samples were collected from patients before starting treatment for TB and frozen at −20°C. Anti‐CCP and IgM RF were evaluated by ELISA. Results The mean (SD) duration of TB related symptoms was 4.4 (1.7) months, 73% had fever, 94% a cough. Rheumatic symptoms were relatively rare: arthralgia (4%), myalgias (4%), eye and mouth dryness (2% and 9%, respectively). Mean (SD) levels of anti‐CCP were significantly increased in patients with TB compared with controls: 44.9 (51) IU v 20 (7.3) IU (p = 0.002). Serum levels >40 U were found in 15/47 (32%) patients compared with 1/39 (2.6%) controls (p = 0.002). Mean (SD) serum levels of IgM RF were significantly increased in patients with TB: 17.8 (19) v 4.3 (5) (p<0.0001). IgM RF was positive (>6 IU) in 29/47 (62%) patients v 1/39 (2.6%) controls (p<0.0001). Conclusions A significant proportion of patients with active TB have an increased titre of anti‐CCP and IgM RF. PMID:16361276

  13. 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

  14. Impact of different body positions on bioelectrical activity of the pelvic floor muscles in nulliparous continent women.

    PubMed

    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.

  15. 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.

  16. Intentional Medication Non-Adherence Due to Interactive Toxicity Beliefs among HIV Positive Active Drug Users

    PubMed Central

    Kalichman, Seth C.; Kalichman, Moira O.; Cherry, Charsey; Hoyt, Ginger; Washington, Christopher; Grebler, Tamar; Merely, Cindy; Welles, Brandi

    2015-01-01

    Drug use poses significant challenges to medical management of HIV infection. While most research has focused on the influence of intoxication on unintentional adherence to HIV treatment, drug use may also lead to intentional non-adherence, particularly when individuals believe that mixing medications with drugs is harmful. This study examined whether interactive toxicity beliefs predict non-adherence to antiretroviral therapy (ART) over a prospective period of adherence monitoring. Men and women living with HIV who screened positive for drug use and were being treated with ART (N=530) completed computerized self-interviews, three prospective unannounced pill counts to measure ART adherence, provided urine specimens for drug screening, and HIV viral load results from medical records. Results showed that 189 (35%) participants indicated that they intentionally miss their ART when they are using drugs. These participants also reported common beliefs regarding the perceived hazards of mixing HIV medications with alcohol and other drugs. Multivariable models that controlled for demographic and health characteristics, as well as frequency of alcohol use, showed that intentional non-adherence predicted poorer ART adherence over the prospective month and also predicted poorer treatment outcomes as indexed by unsuppressed HIV viral load. These findings extend previous research to show that interactive toxicity beliefs and intentional non-adherence play a significant role in medication non-adherence for a substantial number of people living with HIV and should be actively addressed in HIV clinical care. PMID:26226250

  17. 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.

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

    NASA Astrophysics Data System (ADS)

    Pierre Auger Collaboration; Abraham, J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez-Muñiz, J.; Ambrosio, M.; Anchordoqui, L.; Andringa, S.; Anzalone, A.; Aramo, C.; Argirò, S.; Arisaka, K.; Armengaud, E.; Arneodo, F.; Arqueros, F.; Asch, T.; Asorey, H.; Assis, P.; Atulugama, B. S.; Aublin, J.; Ave, M.; Avila, G.; Bäcker, T.; Badagnani, D.; Barbosa, A. F.; Barnhill, D.; Barroso, S. L. C.; Bauleo, P.; Beatty, J. J.; Beau, T.; Becker, B. R.; Becker, K. H.; Bellido, J. A.; Benzvi, S.; Berat, C.; Bergmann, T.; Bernardini, P.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Blasi, P.; Bleve, C.; Blümer, H.; Boháčová, M.; Bonifazi, C.; Bonino, R.; Brack, J.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Burton, R. E.; Busca, N. G.; Caballero-Mora, K. S.; Cai, B.; Camin, D. V.; Caramete, L.; Caruso, R.; Carvalho, W.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chye, J.; Clay, R. W.; Colombo, E.; Conceição, R.; Connolly, B.; Contreras, F.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Donato, C.; de Jong, S. J.; de La Vega, G.; de Mello, W. J. M.; de Mello Neto, J. R. T.; de Mitri, I.; de Souza, V.; Del Peral, L.; Deligny, O.; Della Selva, A.; Delle Fratte, C.; Dembinski, H.; di Giulio, C.; Diaz, J. C.; Diep, P. N.; Dobrigkeit, C.; D'Olivo, J. C.; Dong, P. N.; Dornic, D.; Dorofeev, A.; Dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Duvernois, M. A.; Engel, R.; Epele, L.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; San Luis, P. Facal; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferrer, F.; Ferry, S.; Fick, B.; Filevich, A.; Filipčič, A.; Fleck, I.; Fracchiolla, C. E.; Fulgione, W.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Garrido, X.; Geenen, H.; Gelmini, G.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Herrero, R.; Gonçalves, P.; Gonçalves Do Amaral, M.; Gonzalez, D.; Gonzalez, J. G.; González, M.; Góra, D.; Gorgi, A.; Gouffon, P.; Grassi, V.; Grillo, A. F.; Grunfeld, C.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Gutiérrez, J.; Hague, J. D.; Hamilton, J. C.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Hauschildt, T.; Healy, M. D.; Hebbeker, T.; Hebrero, G.; Heck, D.; Hojvat, C.; Holmes, V. C.; Homola, P.; Hörandel, J.; Horneffer, A.; Horvat, M.; Hrabovský, M.; Huege, T.; Hussain, M.; Iarlori, M.; Insolia, A.; Ionita, F.; Italiano, A.; Kaducak, M.; Kampert, K. H.; Karova, T.; Kégl, B.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapik, R.; Knapp, J.; Koang, D.-H.; Krieger, A.; Krömer, O.; Kuempel, D.; Kunka, N.; Kusenko, A.; La Rosa, G.; Lachaud, C.; Lago, B. L.; Lebrun, D.; Lebrun, P.; Lee, J.; de Oliveira, M. A. Leigui; Letessier-Selvon, A.; Leuthold, M.; Lhenry-Yvon, I.; López, R.; Lopez Agüera, A.; Lozano Bahilo, J.; García, R. Luna; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mancarella, G.; Manceñido, M. E.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Falcon, H. R. Marquez; Martello, D.; Martínez, J.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; McCauley, T.; McEwen, M.; McNeil, R. R.; Medina, M. C.; Medina-Tanco, G.; Meli, A.; Melo, D.; Menichetti, E.; Menschikov, A.; Meurer, Chr.; Meyhandan, R.; Micheletti, M. I.; Miele, G.; Miller, W.; Mollerach, S.; Monasor, M.; Ragaigne, D. Monnier; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Morris, C.; Mostafá, M.; Muller, M. A.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Newman-Holmes, C.; Newton, D.; Nhung, P. T.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Ohnuki, T.; Olinto, A.; Olmos-Gilbaja, V. M.; Ortiz, M.; Ortolani, F.; Ostapchenko, S.; Otero, L.; Pacheco, N.; Selmi-Dei, D. Pakk; Palatka, M.; Pallotta, J.; Parente, G.; Parizot, E.; Parlati, S.; Pastor, S.; Patel, M.; Paul, T.; Pavlidou, V.; Payet, K.; Pech, M.; PȩKala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Petrera, S.; Petrinca, P.; Petrov, Y.; Pichel, A.; Piegaia, R.; Pierog, T.; Pimenta, M.; Pinto, T.; Pirronello, V.; Pisanti, O.; Platino, M.; Pochon, J.; Privitera, P.; Prouza, M.; Quel, E. J.; Rautenberg, J.; Redondo, A.; Reucroft, S.; Revenu, B.; Rezende, F. A. S.; Ridky, J.; Riggi, S.; Risse, M.; Rivière, C.; Rizi, V.; Roberts, M.; Robledo, C.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Roth, M.; Rouillé-D'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E. M.; Sarazin, F.; Sarkar, S.; Sato, R.; Scherini, V.; Schieler, H.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schovánek, P.; Schüssler, F.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Semikoz, D.; Settimo, M.; Shellard, R. C.; Sidelnik, I.; Siffert, B. B.; Sigl, G.; de Grande, N. Smetniansky; Smiałkowski, A.; Šmída, R.; Smith, A. G. K.; Smith, B. E.; Snow, G. R.; Sokolsky, P.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Takahashi, J.; Tamashiro, A.; Tamburro, A.; Taşcău, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Ticona, R.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Peixoto, C. J. Todero; Tomé, B.; Tonachini, A.; Torres, I.; Travnicek, P.; Tripathi, A.; Tristram, G.; Tscherniakhovski, D.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Galicia, J. F. Valdés; Valiño, I.; Valore, L.; van den Berg, A. M.; van Elewyck, V.; Vázquez, R. A.; Veberič, D.; Veiga, A.; Velarde, A.; Venters, T.; Verzi, V.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Voyvodic, L.; Wahlberg, H.; Wainberg, O.; Warner, D.; Watson, A. A.; Westerhoff, S.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Wileman, C.; Winnick, M. G.; Wu, H.; Wundheiler, B.; Yamamoto, T.; Younk, P.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zech, A.; Zepeda, A.; Ziolkowski, M.

    2008-04-01

    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) [Pierre Auger Collaboration, Science 318 (2007) 938]. The correlation has maximum significance for cosmic rays with energy greater than ˜6 × 1019 eV and AGN at a distance less than ˜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 Kuz’min 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.

  20. 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

  1. Paying for outpatient care in rural China: cost escalation under China's New Co-operative Medical Scheme.

    PubMed

    Yang, Wei; Wu, Xun

    2015-03-01

    China's New Co-operative Medical Scheme (NCMS), a government-subsidized health insurance programme, was launched in 2003 in response to deterioration in access to health services in rural areas. Initially designed to cover inpatient care, it has begun to expand its benefit package to cover outpatient care since 2007. The impacts of this initiative on outpatient care costs have raised growing concern, in particular regarding whether it has in fact reduced out-of-pocket (OOP) payments for services among rural participants. This study investigates the impacts on outpatient costs by analysing data from an individual-level longitudinal survey, the China Health and Nutrition Survey, for 2004 and 2009, years shortly before and after NCMS began coverage of outpatient services in 2007. Various health econometrics strategies were employed in the analysis of these data, including the Two-Part Model, the Heckman Selection Model and Propensity Score Matching with the Differences-in-Differences model, to estimate the effects of the 2007 NCMS initiative on per episode outpatient costs. We find that NCMS outpatient coverage starting in 2007 had little impact on reducing its participants' OOP payments for outpatient services. The new coverage may also have contributed to an observed increase in total per episode outpatient costs billed to the insured patients. This increase was more pronounced among village clinics and township health centres-the backbone of the health system for rural residents-than at county and municipal hospitals.

  2. Sympathetic control of skeletal muscle function: possible co-operation between noradrenaline and neuropeptide Y in rabbit jaw muscles.

    PubMed

    Grassi, C; Deriu, F; Roatta, S; Santarelli, R; Azzena, G B; Passatore, M

    1996-07-19

    Stimulation of the cervical sympathetic nerve at 10/s increases by 12.9 +/- 0.7% peak tension of maximal twitches in the directly stimulated jaw muscles and markedly depresses (41.6 +/- 1.3%) the tonic vibration reflex (TVR) elicited in the same muscles by vibration of the mandible. Both effects are not significantly influenced by administration of beta-adrenoceptor antagonists. When both alpha- and beta-adrenergic receptors are blocked, sympathetic stimulation induces a very small increase in twitch tension (3.8 +/- 0.7%), while no detectable change in the TVR is observed. Close arterial injection of alpha 1-adrenoceptor agonist phenylephrine mimics the effects induced by sympathetic stimulation on twitch tension and TVR, dose-dependently. The noradrenaline co-transmitter neuropeptide Y also produces a long-lasting, dose-dependent increase in the twitch tension which is unaffected by blockade of adrenergic receptors as well as of the neuromuscular junctions. Contribution of neuropeptide Y to the sympathetically-induced reduction of the stretch reflex is not clearly demonstrated. These data suggest that co-operation between noradrenaline and neuropeptide Y may be effective in determining sympathetic modulation of skeletal muscle function.

  3. Co-operative Bmp- and Fgf-signaling inputs convert skin wound healing to limb formation in urodele amphibians.

    PubMed

    Makanae, Aki; Mitogawa, Kazumasa; Satoh, Akira

    2014-12-01

    Urodele amphibians have remarkable organ regeneration capability, and their limb regeneration capability has been investigated as a representative phenomenon. In the early 19th century, nerves were reported to be an essential tissue for the successful induction of limb regeneration. Nerve substances that function in the induction of limb regeneration responses have long been sought. A new experimental system called the accessory limb model (ALM) has been established to identify the nerve factors. Skin wounding in urodele amphibians results in skin wound healing but never in limb induction. However, nerve deviation to the wounded skin induces limb formation in ALM. Thus, nerves can be considered to have the ability to transform skin wound healing to limb formation. In the present study, co-operative Bmp and Fgf application, instead of nerve deviation, to wounded skin transformed skin wound healing to limb formation in two urodele amphibians, axolotl (Ambystoma mexicanum) and newt (Pleurodeles waltl). Our findings demonstrate that defined factors can induce homeotic transformation in postembryonic bodies of urodele amphibians. The combination of Bmp and Fgf(s) may contribute to the development of novel treatments for organ regeneration.

  4. Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro

    PubMed Central

    Wu, Yaoxing; Liu, Qingxiang; Zhou, Jie; Xie, Weihong; Chen, Cheng; Wang, Zefang; Yang, Haitao; Cui, Jun

    2017-01-01

    Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFNβ signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK–STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death. Furthermore, co-operation of NS1, NS4B and NS2B3 further enhances viral infection by blocking IFN-induced autophagic degradation of NS2B3. Hence, our study reveals a novel antagonistic system employing multiple ZIKV nonstructural proteins in restricting the innate antiviral responses. PMID:28373913

  5. Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro.

    PubMed

    Wu, Yaoxing; Liu, Qingxiang; Zhou, Jie; Xie, Weihong; Chen, Cheng; Wang, Zefang; Yang, Haitao; Cui, Jun

    2017-01-01

    Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFNβ signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK-STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death. Furthermore, co-operation of NS1, NS4B and NS2B3 further enhances viral infection by blocking IFN-induced autophagic degradation of NS2B3. Hence, our study reveals a novel antagonistic system employing multiple ZIKV nonstructural proteins in restricting the innate antiviral responses.

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

    PubMed Central

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

    2016-01-01

    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

  7. 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.

  8. Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity

    PubMed Central

    Wahl, Angela; Baker, Caroline; Spagnuolo, Rae Ann; Stamper, Lisa W.; Fouda, Genevieve G.; Permar, Sallie R.; Hinde, Katie; Kuhn, Louise; Bode, Lars; Aldrovandi, Grace M.

    2015-01-01

    ABSTRACT Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy. IMPORTANCE Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants

  9. In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria.

    PubMed

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

    2013-12-01

    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.

  10. American College of Sports Medicine. Position Stand. Physical activity, physical fitness, and hypertension.

    PubMed

    1993-10-01

    Hypertension is present in epidemic proportions in adults of industrialized societies and is associated with a markedly increased risk of developing numerous cardiovascular pathologies. There is a continuing debate as to the efficacy of aggressive pharmacological therapy in individuals with mild to moderate elevations in blood pressure. This has led to a search for nonpharmacological therapies, such as exercise training, for these individuals. The available evidence indicates that endurance exercise training by individuals at high risk for developing hypertension will reduce the rise in blood pressure that occurs with time. Thus, it is the position of the American College of Sports Medicine that endurance exercise training is recommended as a nonpharmacological strategy to reduce the incidence of hypertension in susceptible individuals. A large number of studies indicate that endurance exercise training will elicit a 10 mm Hg average reduction in both systolic and diastolic blood pressures in individuals with mild essential hypertension (blood pressures 140-180/90-105 mm Hg). Endurance exercise training also has the capacity to improve other risk factors for cardiovascular disease in hypertensive individuals. Endurance exercise training appears to elicit even greater reductions in blood pressure in patients with secondary hypertension due to renal dysfunction. The mode (large muscle activities), frequency (3-5 d.wk-1), duration (20-60 min), and intensity (50-85% of maximal oxygen uptake) of the exercise recommended to achieve this effect are generally the same as those prescribed for developing and maintaining cardiovascular fitness in healthy adults. Exercise training at somewhat lower intensities (40-70% VO2max) appears to lower blood pressure as much, or more, than exercise at higher intensities, which may be important in specific hypertensive populations. Physically active and fit individuals with hypertension have markedly lower rates of mortality than

  11. Activation and repression functions of an SR splicing regulator depend on exonic versus intronic-binding position.

    PubMed

    Shen, Manli; Mattox, William

    2012-01-01

    SR proteins and related factors play widespread roles in alternative pre-mRNA splicing and are known to promote splice site recognition through their Arg-Ser-rich effector domains. However, binding of SR regulators to some targets results in repression of splice sites through a distinct mechanism. Here, we investigate how activated and repressed targets of the Drosophila SR regulator Transformer2 elicit its differing effects on splicing. We find that, like activation, repression affects early steps in the recognition of splice sites and spliceosome assembly. Repositioning of regulatory elements reveals that Tra2 complexes that normally repress splicing from intronic positions activate splicing when located in an exon. Protein tethering experiments demonstrate that this position dependence is an intrinsic property of Tra2 and further show that repression and activation are mediated by separate effector domains of this protein. When other Drosophila SR factors (SF2 and Rbp1) that activate splicing from exonic positions were tethered intronically they failed to either activate or repress splicing. Interestingly, both activities of Tra2 favor the exonic identity of the RNA sequences that encompass its binding sites. This suggests a model in which these two opposite functions act in concert to define both the position and extent of alternatively spliced exons.

  12. 22 CFR 42.24 - Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of Intercountry Adoption and the Intercountry Adoption Act... Limitations of INA 201 and 202 § 42.24 Adoption under the Hague Convention on Protection of Children and...

  13. 22 CFR 42.24 - Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of Intercountry Adoption and the Intercountry Adoption Act... Limitations of INA 201 and 202 § 42.24 Adoption under the Hague Convention on Protection of Children and...

  14. 22 CFR 42.24 - Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of Intercountry Adoption and the Intercountry Adoption Act... Limitations of INA 201 and 202 § 42.24 Adoption under the Hague Convention on Protection of Children and...

  15. 22 CFR 42.24 - Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of Intercountry Adoption and the Intercountry Adoption Act... Limitations of INA 201 and 202 § 42.24 Adoption under the Hague Convention on Protection of Children and...

  16. 22 CFR 42.24 - Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Adoption under the Hague Convention on Protection of Children and Co-operation in Respect of Intercountry Adoption and the Intercountry Adoption Act... Limitations of INA 201 and 202 § 42.24 Adoption under the Hague Convention on Protection of Children and...

  17. Perceptions of Student Teachers towards the Effectiveness of Co-Operating Teachers, School Principals and University Supervisors Participating in the Teacher Education Program in Jordan

    ERIC Educational Resources Information Center

    Albasheer, Akram; Khasawneh, Samer; Nabah, Abdallah Abu; Hailat, Salah

    2008-01-01

    The primary purpose of this study was to determine perceptions of student teachers regarding the effectiveness of university supervisors, school principals and co-operating teachers participating in the teacher education program at the Hashemite University in Jordan. A total of 120 student teachers participated in the study by completing the…

  18. 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…

  19. 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…

  20. 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

  1. 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

  2. Amino acid catalyzed bulk-phase gelation of organoalkoxysilanes via a transient co-operative self-assembly.

    PubMed

    Shen, Shukun; Hu, Daodao; Sun, Peipei; Zhang, Xiaoru; Parikh, Atul N

    2009-10-15

    We report acceleration in the rate of bulk phase gelation of an organoalkoxysilane, 3-methacryloxypropyltrimethoxysilane (MAPTMS), in the presence of an amphiphilic additive, N-phenyl glycine (NPG). The MAPTMS gelation occurs within 30 min in the presence of 0.5 wt % NPG, which took several months in the absence of NPG. Using a combination of ATR-FT IR, (29)Si NMR, (1)H NMR, viscosity analysis, SEM, UV-vis, and pi-A isotherm measurements, we elucidate the molecular-level details of the structural changes during NPG-catalyzed MPTMS gelation rate. On the basis of these results, we propose a gelation mechanism in which a transient cooperative self-assembly process fosters hydrolysis and retards early condensation thereby promoting the formation of extended three-dimensionally cross-linked gels. Specifically, the amphiphilic character of the hydrolysis product of MAPTMS, consisting of a hydrophobic tail R = -CH(2)CH(2)CH(2)O(CO)C(CH(3)) horizontal lineCH(2) and a hydrophilic Si-OH headgroup, promotes micelle formation at high MAPTMS/water ratio. NPG readily inserts within these micelles thus retarding the topotactic condensation of silanols at the micellar surface. This in turn allows for a more complete hydrolysis of Si-OCH(3) groups prior to condensation in MAPTMS. With increased silanol concentration at the micellar periphery, a delayed condensation phase initiates. This formation of a covalently bonded Si-O-Si framework (and possibly also the formation of the methanol byproduct) likely destabilizes the micellar motif thus promoting its transformation into condensed mesophases (e.g., lamellar microstructure) upon gelation. Because of the generality of this transient and co-operative organic-inorganic self-assembly between hydrolyzed amphiphilic organoalkoxysilanes and surfactant-like amino acid additives, we envisage applications in controlling bulk phase gelation of many chain-substituted organoalkoxysilanes.

  3. International co-operation in the development of a new paradigm for the emissions inventory program in Mexico

    SciTech Connect

    Snow, C.; Fields, P.; Oliver, W.R.; Figueroa, V.H.P.; Sarmiento, J.

    1999-07-01

    In 1983, the governments of both the US of America and the United Mexican States signed the Agreement on Co-Operation for the Protection and Improvement of the Environment in the Border Area, otherwise known as the La Paz Agreement. Through this agreement both the US and Mexico agreed to cooperate in the field of environmental protection in the border area on the basis of equality, reciprocity and mutual benefit. Both countries agreed to coordinate their efforts, in conformity with their own national legislation and existing bilateral agreements, to address problems of air, land and water pollution in the border area. In the US, the Western Governors' Association (WGA) coordinated with Mexico's environmental agency, the National Institute of Ecology (INE), to develop a new paradigm for INE's air emissions inventory program. The development of this program began with a review of INE's current system and how it could be modified to reduce the air pollution in the country's major metropolitan areas. The primary objectives of this program are to build capacity in Mexico for developing emission inventories, and develop and test emission inventory methods developed especially for Mexican sources. In addition to the WGA's contracted professional consultants, a Binational Advisory Committee, composed of qualified emissions inventory professionals in both Mexico and the US, was organized to review, comment and make recommendations during the development of the program. Through their collective expertise in emissions inventories, the participants in this process have been successful in developing a series of training manuals designed for INE's engineers to implement the new emissions inventory program throughout Mexico. Other accomplishments of this program include conducting training of University Autonama Metropolitan faculty, INE staff, and Mexican industry representatives.

  4. 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

  5. High Caesarean section rate in rural China: is it related to health insurance (New Co-operative Medical Scheme)?

    PubMed

    Long, Qian; Klemetti, Reija; Wang, Yang; Tao, Fangbiao; Yan, Hong; Hemminki, Elina

    2012-08-01

    The epidemic of Caesarean section (CS) is worldwide, and it has been argued that it is mainly due to non-medical factors, including healthcare financing patterns. We investigated the use of CS in rural China and the related factors, particularly health insurance in the form of the New Co-operative Medical Scheme introduced in 2003. A cross-sectional survey of women who gave birth in 2008-2009 was conducted in five rural counties in central and western China. Of the 5049 new mothers, 73% were interviewed. The association between health insurance coverage and self-reported CS (divided into emergency and non-emergency CS) were examined by cross-tabulation and logistic regression, adjusting for maternal age, education, occupation, household income, previous abortions, parity and type of birth health facility. We found that 46% of all births (3550) were CSs, with 13% having an emergency and 33% a non-emergency CS. Women reported that half of the non-emergency CSs were recommended by a doctor and half were requested by themselves. In those counties with mid-range CS rates (28%-63%), health insurance coverage was associated with having CS, and particularly with having non-emergency CS. In those counties with the highest (82%) and lowest (13%) rate, there was no statistically significant association. The findings suggest that health insurance coverage may have facilitated the overuse of CS. Further studies are needed to develop appropriate interventions to reduce non-medically indicated CS, focussing on payment mechanisms, healthcare provider practice patterns, and maternal requests.

  6. False-positive scalp activity in 131I imaging associated with hair coloring.

    PubMed

    Yan, Di; Doss, Mohan; Mehra, Ranee; Parsons, Rosaleen B; Milestone, Barton N; Yu, Jian Q

    2013-03-01

    A patient with metastatic papillary thyroid carcinoma (after surgical resection of tumor and positive lymph nodes) undergoing thyroid ablation therapy with (131)I is described. Whole-body scintigraphy was performed 1 wk after ablation therapy to evaluate the presence of residual disease. The whole-body images demonstrated an artifact caused by tracer accumulation in the patient's scalp related to recent hair coloring. Common etiologies of false-positive (131)I scintigraphic findings are briefly reviewed. The importance of taking preventative measures to decrease the number of false-positive findings and recognizing these findings when they occur is discussed.

  7. Effect of the kangaroo position on the electromyographic activity of preterm children: a follow-up study

    PubMed Central

    2013-01-01

    Background One of the components of the Kangaroo Method (KM) is the adoption of the Kangaroo Position. The skin-to-skin contact and the vertical position the child adopts when in this position may provide sensorial, vestibular and postural stimuli for the newborn. The Kangaroo Position may encourage vestibular stimuli and a flexed posture of the limbs, suggesting the hypothesis that the Kangaroo Position may have an impact on flexor muscle tone. The effect of these stimuli on the motor features of the newborn has not been the subject of much investigation. No study has yet been conducted to determine whether the Kangaroo Position may progressively increase electromyographic activity or whether this increase persists until term-equivalent age. The aim of this study was to evaluate the effect of the Kangaroo Position on the electromyographic activity of preterm children. Method A follow-up study was carried out between July and November 2011 at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife-Brazil, using a sample of 30 preterm children. Surface Eletromyography (SEMG) was used to investigate the muscle activity of biceps brachii. The electromyographic readings were taken immediately before (0 h) and after 24 h, 48 h, 72 h, 96 h of application of the Kangaroo Position as well as at the term equivalent age in each baby. Electromyographic activity was analyzed using the Root Mean Square (RMS) and the mean values of the times were analyzed by way of analysis of variance for repeated measures and the Tukey test. Results Electromyographic activity of the biceps brachii varied and increased over the whole 96h period (RMS:0 h = 36.5 and 96 h = 52.9) (F(5.174) = 27.56; p < 0.001) and remained constant thereafter (RMS: term-equivalent age = 54.2). The correlations between the corrected age and the values for electromyographic activity did not show any statistical significance. Conclusion The Kangaroo Position leads to a growing

  8. Oral Cnm-positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment

    PubMed Central

    Watanabe, Isao; Kuriyama, Nagato; Miyatani, Fumitaro; Nomura, Ryota; Naka, Shuhei; Nakano, Kazuhiko; Ihara, Masafumi; Iwai, Komei; Matsui, Daisuke; Ozaki, Etsuko; Koyama, Teruhide; Nishigaki, Masaru; Yamamoto, Toshiro; Tamura, Aiko; Mizuno, Toshiki; Akazawa, Kentaro; Takada, Akihiro; Takeda, Kazuo; Yamada, Kei; Nakagawa, Masanori; Tanaka, Tokutaro; Kanamura, Narisato; Friedland, Robert P.; Watanabe, Yoshiyuki

    2016-01-01

    Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction. PMID:27934941

  9. This ought to be good: brain activity accompanying positive and negative expectations and outcomes.

    PubMed

    Liao, Yu; Gramann, Klaus; Feng, Wenfeng; Deák, Gedeon O; Li, Hong

    2011-10-01

    The current study employed a modified gambling task, in which probabilistic cues were provided to elicit positive or negative expectations. Event-related potentials (ERPs) to "final outcome" and "probabilistic cues" were analyzed. Difference waves between the negative condition and the corresponding positive condition were examined. The results confirm that feedback related negativity (FRN) amplitude is modulated by the interaction of outcome valence and expectancy by showing larger FRN difference waves for unexpected than expected outcomes. More interestingly, the difference wave between ERPs elicited by positive and negative expectations showed a negative deflection, with a frontal midline source density around 280 ms after onset of the predictive cue. Negative expectations were associated with larger FRN amplitudes than positive expectations. This suggests that FRN is elicited by probabilistic cues to pending outcomes.

  10. Canadian Society for Exercise Physiology position stand: Benefit and risk for promoting childhood physical activity.

    PubMed

    Longmuir, Patricia E; Colley, Rachel C; Wherley, Valerie A; Tremblay, Mark S

    2014-11-01

    Current guidelines recommend children accumulate 60 min of daily physical activity; however, highly publicized sudden-death events among young athletes raise questions regarding activity safety. An expert group convened (June 2012) to consider the safety of promoting increased physical activity for children, and recommended the publication of an evidence-based statement of current knowledge regarding the benefits and risks of physical activity for children. Recommendations for encouraging physical activity while maximizing the opportunity to identify children who have been prescribed a physical activity restriction include (1) professionals and (or) researchers that encourage children to change the type of physical activity or to increase the frequency, intensity, or duration of their activity should inquire whether a child has primary healthcare provider-prescribed activity limitations before the child's activity participation changes; (2) physical activity researchers should prioritize the development of evidence regarding the benefits and risks of childhood physical activity and inactivity, particularly data on the risks of sedentary lifestyles and physical activity-associated injury risks that accounts for the amount of activity performed, and the effectiveness of current risk-management strategies and screening approaches; (3) professionals and researchers should prioritize the dissemination of information regarding the benefits of physical activity and the risks of sedentary behaviour in children; and (4) parents and professionals should encourage all children to accumulate at least 60 min of physical activity daily. The recommendations are established as a minimum acceptable standard that is applicable to all physical activity opportunities organized for children, whether those opportunities occur in a community, school, or research setting.

  11. 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.

  12. 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

  13. In vitro activity of paldimycin (U-70138F) against gram-positive bacteria isolated from patients with cancer.

    PubMed Central

    Rolston, K V; LeBlanc, B; Ho, D H; Bodey, G P

    1987-01-01

    The in vitro activity of paldimycin, a novel antimicrobial agent, was compared with that of vancomycin against 306 gram-positive isolates (representing 12 bacterial species) obtained from patients with cancer. Paldimycin had lower MICs for 90% of isolates than vancomycin did against most isolates tested. Its activity, however, was medium and pH dependent, being greatest in Nutrient broth at a pH of 6.8. PMID:3606069

  14. Wrist skin temperature, motor activity, and body position as determinants of the circadian pattern of blood pressure.

    PubMed

    Blazquez, A; Martinez-Nicolas, A; Salazar, F J; Rol, M A; Madrid, J A

    2012-07-01

    Although the circadian blood pressure (BP) pattern has been extensively studied, the determinants of this rhythm are not fully understood. Peripheral vasodilatation is a regulatory mechanism for BP maintenance. However, it remains to be established whether the increase of nocturnal distal skin temperature associated with heat loss could also reflect the dipping status. For the first time, this paper investigates the relationship between BP and skin wrist temperature (WT), to evaluate whether the WT circadian rhythm can serve as screening procedure to detect dipping/non-dipping BP patterns. In addition, the authors compare the relationship between WT and other variables previously described as determinants of the BP pattern, such as physical activity and body position. Measurements of WT, motor activity, and body position for 5 d, plus ambulatory BP for 24-h during that span, were obtained from 28 diurnally active normotensive volunteers. WT was negatively correlated, whereas activity and body position were positively correlated, with systolic and diastolic BPs. However, these relationships were stronger during the rest than activity phase. In addition, a 78.6% concordance was detected between the observed dips in BP and the predicted BP pattern calculated based on the WT rhythm. Thus, these results suggest that the increase in WT produced by heat loss during the rest phase through peripheral skin blood vessels is the result of blood vessel vasodilatation reflexes in response to a shift from a standing to a supine position, together with shift in the circadian sympathetic/parasympathetic balance (nocturnal parasympathetic activation). In conclusion, WT could be considered as a potential new screening procedure to implement the diagnosis of non-dipping BP pattern.

  15. Potent antitumor activity of quinolone compounds with an unsaturated aminoazabicyclo group at the C-7 position of the quinolone ring.

    PubMed

    Arakawa, H; Mano, E; Hakoda, N; Yoshinari, T; Nakagawa, S; Okura, A

    1996-04-01

    Relationships between the substituents on the quinolone nucleus of 2 and related compounds and their biological activities were studied. 2, 3 and 1 carrying a (1R, 2R, 6R)-2-amino-8-azabicyclo[4.3.0.]non-3-en-8-yl group at the C-7 position increased the rate of formation of DNA-protein complexes in cells, and inhibited the growth of tumor cells more strongly than the compounds with other substituents. The introduction of a fluorine atom or a methoxy group at the 8-position and an amino group at the 5-position increased the activity still further. The three compounds listed were all effective against P388 leukemia in mice. Subcutaneous injection of 2 at 2 mg/kg strongly suppressed the growth of human MX-1 breast cancer cells in nude mice. 1 has various functional groups that increase the cytotoxic potential of quinolone derivatives: a (1R, 2R, 6R)-2-amino-8-azabicyclo[4.3.0.]non-3-en-8-yl moiety at C-7, a cyclopropyl group at the 1-position, fluorine atoms at the 6- and 8-positions, and an amino group at the 5-position of the quinoline carboxylic acid. These data suggest that this series of compounds provide good models for the further design of potent antitumor quinolones.

  16. 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 intervention…

  17. Positioning Australia's Contemporary Health and Physical Education Curriculum to Address Poor Physical Activity Participation Rates by Adolescent Girls

    ERIC Educational Resources Information Center

    Usher, Wayne; Edwards, Allan; Cudmore, Laura

    2016-01-01

    Background: Given the wealth of research identifying how schools are in a strong position to promote physical activity (PA) among children, it would be reasonable to suggest that initial experiences of physical education and school sport are critical factors influencing whether a student will develop a healthy relationship to PA. However, research…

  18. Counseling Special Students: An Activity Book for Encouraging Positive Interaction Between Non-Handicapped and Handicapped Students.

    ERIC Educational Resources Information Center

    Loucks, Hazel

    The activity book is designed to assist school counselors in preparing nonhandicapped persons to interact in a positive manner with the handicapped. An introductory section defines the term handicapped, offers program management guidelines, considers needs assessment, and describes three counseling models (peer helper, classroom guidance, and…

  19. NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

    PubMed Central

    Xiong, Ying; Wang, Yan; Zheng, Junfang; Zhao, Yuan; Tao, Tao; Wang, Qiqi; Liu, Hua; Wang, Songlin; Jiang, Wen G.; He, Junqi

    2016-01-01

    G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC. PMID:27448983

  20. The Effect of Varying Biting Position on Relative Jaw Muscle EMG activity

    DTIC Science & Technology

    1988-09-01

    goal is to protect the temporomandibular joint tissues and therefore minimizes joint force. The second hypothesis is that the system maximizes...modalities for some temporomandibular disorders . Several models have been proposed, but very little experimental work has been accomplished to...tenderness seen in temporomandibular disorder patients. Correlation of wear facet patterns and specific mandibular positions during bruxing with

  1. 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…

  2. 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…

  3. 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…

  4. Analysing Third Generation Activity Systems: Labour-Power, Subject Position and Personal Transformation

    ERIC Educational Resources Information Center

    Daniels, Harry; Warmington, Paul

    2007-01-01

    Purpose: The purpose of this paper is to describe how Engestrom's "third generation" activity theory, with its emphasis on developing conceptual tools to understand dialogues, multiple perspectives and networks of interacting activity systems, has informed research into professional learning in multiagency service settings in England.…

  5. 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…

  6. Antigenicity of UV radiation-induced murine tumors correlates positively with the level of adenosine deaminase activity.

    PubMed

    Aukerman, S L; Fidler, I J

    1987-01-01

    The specific activities of adenosine deaminase (ADA) in 16 murine tumor cell lines derived from seven UV light-induced neoplasms (melanoma and fibrosarcoma) were determined. In each case, the specific activity of ADA correlated positively with the antigenicity of the tumor cells. Highly antigenic cell lines that regress upon introduction into syngeneic hosts had on average 4- to 6-fold higher ADA specific activities than cell lines of low antigenicity that grow progressively in syngeneic hosts. The antigenic differences are probably not related to intracellular cAMP levels, as the level of cAMP differed only 2-fold between the two groups of cell lines.

  7. 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

  8. In vitro activities of a new lipopeptide, HMR 1043, against susceptible and resistant gram-positive isolates.

    PubMed

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

    2003-09-01

    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.

  9. Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGluR5) attenuate microglial activation.

    PubMed

    Xue, Fengtian; Stoica, Bogdan A; Hanscom, Marie; Kabadi, Shruti V; Faden, Alan I

    2014-01-01

    Traumatic brain injury causes progressive neurodegeneration associated with chronic microglial activation. Recent studies show that neurodegeneration and neuroinflammation after traumatic brain injury can be inhibited as late as one month in animals by the activation of the metabotropic glutamate receptor 5 in microglia using (RS)-2-chloro-5- hydroxy-phenylglycine. However, the therapeutic potential of this agonist is limited due to its relatively weak potency and brain permeability. To address such concerns, we evaluated the anti-inflammatory activities of several positive allosteric modulators using various in vitro assays, and found that 3,3'-difluorobenzaldazine, 3-cyano-N-(1,3-diphenyl-1H-pyrazol- 5-yl)benzamide and 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl)benzamide showed significantly improved potency which makes them potential lead compounds for further development of positive allosteric modulators for the treatment of traumatic brain injury.

  10. 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.

  11. 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

  12. Persistent neural activity during the maintenance of spatial position in working memory.

    PubMed

    Srimal, Riju; Curtis, Clayton E

    2008-01-01

    The mechanism for the short-term maintenance of information involves persistent neural activity during the retention interval, which forms a bridge between the cued memoranda and its later contingent response. Here, we used event-related functional magnetic resonance imaging to identify cortical areas with activity that persists throughout working memory delays with the goal of testing if such activity represents visuospatial attention or prospective saccade goals. We did so by comparing two spatial working memory tasks. During a memory-guided saccade (MGS) task, a location was maintained during a delay after which a saccade was generated to the remembered location. During a spatial item recognition (SIR) task identical to MGS until after the delay, a button press indicated whether a newly cued location matched the remembered location. Activity in frontal and parietal areas persisted above baseline and was greater in the hemisphere contralateral to the cued visual field. However, delay-period activity did not differ between the tasks. Notably, in the putative frontal eye field (FEF), delay period activity did not differ despite that the precise metrics of the memory-guided saccade were known during the MGS delay and saccades were never made in SIR. Persistent FEF activity may therefore represent a prioritized attentional map of space, rather than the metrics for saccades.

  13. 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

  14. Species-Specific Activity of HIV-1 Vpu and Positive Selection of Tetherin Transmembrane Domain Variants

    PubMed Central

    McNatt, Matthew W.; Zang, Trinity; Hatziioannou, Theodora; Bartlett, Mackenzie; Fofana, Ismael Ben; Johnson, Welkin E.; Neil, Stuart J. D.; Bieniasz, Paul D.

    2009-01-01

    Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins. PMID:19214216

  15. Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants.

    PubMed

    McNatt, Matthew W; Zang, Trinity; Hatziioannou, Theodora; Bartlett, Mackenzie; Fofana, Ismael Ben; Johnson, Welkin E; Neil, Stuart J D; Bieniasz, Paul D

    2009-02-01

    Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins.

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

    PubMed Central

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

    2015-01-01

    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 Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-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 Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  17. Hip range of motion during daily activities in patients with posterior pelvic tilt from supine to standing position.

    PubMed

    Tamura, Satoru; Miki, Hidenobu; Tsuda, Kosuke; Takao, Masaki; Hattori, Asaki; Suzuki, Naoki; Yonenobu, Kazuo; Sugano, Nobuhiko

    2015-04-01

    In most patients with hip disorders, the anterior pelvic plane (APP) sagittal tilt does not change from supine to standing position. However, in some patients, APP sagittal tilt changes more than 10° posteriorly from supine to standing position. The purpose of this study was to both examine APP sagittal tilt and investigate the hip flexion and extension range of motion (ROM) required during daily activities in these atypical patients. Patient-specific 4-dimensional (4D) motion analysis was performed for 50 hips from 44 patients who had undergone total hip arthroplasty. All patients divided into two categories, such as atypical patients for whom the pelvis tilted more than 10° posteriorly from supine to standing position preoperatively (19 hips from 18 patients) and the remaining typical patients (31 hips from 26 patients). The required hip flexion and extension angles did not differ significantly between atypical patients and typical patients. In conclusion, the hip flexion ROM during deep bending activities and hip extension ROM during extension activities required in those atypical patients with pelvic tilt more than 10° backward from supine to standing position did not shift in the direction of extension.

  18. “Stepping Up” Activity Poststroke: Ankle-Positioned Accelerometer Can Accurately Record Steps During Slow Walking

    PubMed Central

    Klassen, Tara D.; Simpson, Lisa A.; Lim, Shannon B.; Louie, Dennis R.; Parappilly, Beena; Sakakibara, Brodie M.; Zbogar, Dominik

    2016-01-01

    Background As physical activity in people poststroke is low, devices that monitor and provide feedback of walking activity provide motivation to engage in exercise and may assist rehabilitation professionals in auditing walking activity. However, most feedback devices are not accurate at slow walking speeds. Objective This study assessed the accuracy of one accelerometer to measure walking steps of community-dwelling individuals poststroke. Design This was a cross-sectional study. Methods Two accelerometers were positioned on the nonparetic waist and ankle of participants (N=43), and walking steps from these devices were recorded at 7 speeds (0.3–0.9 m/s) and compared with video recordings (gold standard). Results When positioned at the waist, the accelerometer had more than 10% error at all speeds, except 0.8 and 0.9 m/s, and numerous participants recorded zero steps at 0.3 to 0.5 m/s. The device had 10% or less error when positioned at the ankle for all speeds between 0.4 and 0.9 m/s. Limitations Some participants were unable to complete the faster walking speeds due to their walking impairments and inability to maintain the requested walking speed. Conclusions Although not recommended by the manufacturer, positioning the accelerometer at the ankle (compared with the waist) may fill a long-standing need for a readily available device that provides accurate feedback for the altered and slow walking patterns that occur with stroke. PMID:26251478

  19. 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.

  20. 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.

  1. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.

    PubMed

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-08-30

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition.

  2. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity

    PubMed Central

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-01-01

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition. PMID:27527864

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

    PubMed Central

    2016-01-01

    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. Calpain-controlled detachment of major glycoproteins from the cytoskeleton regulates adhesive properties of activated phosphatidylserine-positive platelets.

    PubMed

    Artemenko, Elena O; Yakimenko, Alena O; Pichugin, Alexey V; Ataullakhanov, Fazly I; Panteleev, Mikhail A

    2016-02-15

    In resting platelets, adhesive membrane glycoproteins are attached to the cytoskeleton. On strong activation, phosphatidylserine(PS)-positive and -negative platelet subpopulations are formed. Platelet activation is accompanied by cytoskeletal rearrangement, although the glycoprotein attachment status in these two subpopulations is not clear. We developed a new, flow cytometry-based, single-cell approach to investigate attachment of membrane glycoproteins to the cytoskeleton in cell subpopulations. In PS-negative platelets, adhesive glycoproteins integrin αIIbβ3, glycoprotein Ib and, as shown for the first time, P-selectin were associated with the cytoskeleton. In contrast, this attachment was disrupted in PS-positive platelets; it was retained to some extent only in the small convex regions or 'caps'. It correlated with the degradation of talin and filamin observed only in PS-positive platelets. Calpain inhibitors essentially prevented the disruption of membrane glycoprotein attachment in PS-positive platelets, as well as talin and filamin degradation. With the suggestion that detachment of glycoproteins from the cytoskeleton may affect platelet adhesive properties, we investigated the ability of PS-positive platelets to resist shear-induced breakaway from the immobilized fibrinogen. Shear rates of 500/s caused PS-positive platelet breakaway, but their adhesion stability increased more than 10-fold after pretreatment of the platelets with calpain inhibitor. In contrast, the ability of PS-positive platelets to adhere to immobilized von Willebrand's factor at 100/s was low, but this was not affected by the preincubation of platelets with a calpain inhibitor. Our data suggest that calpain-controlled detachment of membrane glycoproteins is a new mechanism that is responsible for the loss of ability of the procoagulant platelets to resist detachment from thrombi by high shear stress.

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

    PubMed

    Sanders, Gabriel J; Rebold, Michael; Peacock, Corey A; Williamson, Meagan L; Santo, Antonio S; Barkley, Jacob E

    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.

  6. Care of the HIV-positive patient in the emergency department in the era of highly active antiretroviral therapy.

    PubMed

    Venkat, Arvind; Piontkowsky, David M; Cooney, Robert R; Srivastava, Adarsh K; Suares, Gregory A; Heidelberger, Cory P

    2008-09-01

    More than 1 million individuals in the United States are HIV positive, with greater than 40,000 new patients being diagnosed per year. With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients in the United States are living longer. HIV-infected patients receiving HAART now more commonly have noninfectious and nonopportunistic complications of their disease. This review article will discuss the assessment and treatment of HIV-positive patients in the era of HAART, with an emphasis on the noninfectious and changing infectious complications that require emergency care.

  7. Analysis of positions and substituents on genotoxicity of fluoroquinolones with quantitative structure-activity relationship and 3D Pharmacophore model.

    PubMed

    Fengxian, Chen; Reti, Hai

    2017-02-01

    The genotoxicity values of 21 quinolones were studied to establish a quantitative structure-activity relationship model and 3D Pharmacophore model separately for screening essential positions and substituents that contribute to genotoxicity of fluoroquinolones (FQs). A full factor experimental design was performed to analyze the specific main effect and second-order interaction effect of different positions and substituents on genotoxicity, forming a reasonable modification scheme which was validated on typical FQ with genotoxicity and efficacy data. Four positions (1, 5, 7, 8) were screened finally to form the full factorial experimental design which contained 72 congeners in total, illustrating that: the dominant effect of 5 and 7-positions on genotoxicity of FQs is main effect; meanwhile the effect of 1 and 8-positions is a second-order interaction effect; two adjacent positions always have stronger second-order interaction effect and lower genotoxicity; the obtained modification scheme had been validated on typical FQ congeners with the modified compound has a lower genotoxicity, higher synthesis feasibilities and efficacy.

  8. 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

  9. Electromyography activity of the deltoid muscle of the weight-bearing side during shoulder flexion in various weight-bearing positions

    PubMed Central

    Ju, Sung-kwang; Yoo, Won-gyu

    2015-01-01

    [Purpose] This study investigated the deltoid muscle activation during shoulder flexion exercise in various weight-bearing positions. [Subjects] A total of 15 males participated. [Methods] The participants completed three repetitions of shoulder flexion exercises in three positions (prone-on-elbow, quadruped, and standing) with electromyography activity being collected from the exercised. The muscle activations in each position by each exercise were compared using a one-way analysis of variance. [Results] The electromyography activities of the middle and posterior deltoids differed significantly among positions. The prone-on-elbow and quadruped position showed a significantly higher activity than the standing position. There were no significant differences between the prone-on-elbow and quadruped positions. [Conclusion] The deltoid muscles were further strengthened in the low posture positions (prone-on-elbows and quadruped) than in standing. PMID:26644694

  10. The human IL-2 gene promoter can assemble a positioned nucleosome that becomes remodeled upon T cell activation.

    PubMed

    Attema, Joanne L; Reeves, Raymond; Murray, Vincent; Levichkin, Ilya; Temple, Mark D; Tremethick, David J; Shannon, M Frances

    2002-09-01

    Controlled production of the cytokine IL-2 plays a key role in the mammalian immune system. Expression from the gene is tightly regulated with no detectable expression in resting T cells and a strong induction following T cell activation. The IL-2 proximal promoter (+1 to -300) contains many well-defined transcriptional activation elements that respond to T cell stimulation. To determine the role of chromatin structure in the regulation of interleukin-2 gene transcription, nucleosome assembly across the IL-2 promoter region was examined using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a nucleosome that is both translationally and rotationally positioned, spanning some of the major functional control elements. The binding of transcription factors to these elements, with the exception of the architectural protein HMGA1, was occluded by the presence of the nucleosome. Analysis of the chromatin architecture of the IL-2 gene in Jurkat T cells provided evidence for the presence of a similarly positioned nucleosome in vivo. The region encompassed by this nucleosome becomes remodeled following activation of Jurkat T cells. These observations suggest that the presence of a positioned nucleosome across the IL-2 proximal promoter may play an important role in maintaining an inactive gene in resting T cells and that remodeling of this nucleosome is important for gene activation.

  11. Positive reinforcement mediated by midbrain dopamine neurons requires D1 and D2 receptor activation in the nucleus accumbens.

    PubMed

    Steinberg, Elizabeth E; Boivin, Josiah R; Saunders, Benjamin T; Witten, Ilana B; Deisseroth, Karl; Janak, Patricia H

    2014-01-01

    The neural basis of positive reinforcement is often studied in the laboratory using intracranial self-stimulation (ICSS), a simple behavioral model in which subjects perform an action in order to obtain exogenous stimulation of a specific brain area. Recently we showed that activation of ventral tegmental area (VTA) dopamine neurons supports ICSS behavior, consistent with proposed roles of this neural population in reinforcement learning. However, VTA dopamine neurons make connections with diverse brain regions, and the specific efferent target(s) that mediate the ability of dopamine neuron activation to support ICSS have not been definitively demonstrated. Here, we examine in transgenic rats whether dopamine neuron-specific ICSS relies on the connection between the VTA and the nucleus accumbens (NAc), a brain region also implicated in positive reinforcement. We find that optogenetic activation of dopaminergic terminals innervating the NAc is sufficient to drive ICSS, and that ICSS driven by optical activation of dopamine neuron somata in the VTA is significantly attenuated by intra-NAc injections of D1 or D2 receptor antagonists. These data demonstrate that the NAc is a critical efferent target sustaining dopamine neuron-specific ICSS, identify receptor subtypes through which dopamine acts to promote this behavior, and ultimately help to refine our understanding of the neural circuitry mediating positive reinforcement.

  12. 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

  13. Activation of phenylalanine hydroxylase induces positive cooperativity toward the natural cofactor.

    PubMed

    Gersting, Søren W; Staudigl, Michael; Truger, Marietta S; Messing, Dunja D; Danecka, Marta K; Sommerhoff, Christian P; Kemter, Kristina F; Muntau, Ania C

    2010-10-01

    Protein misfolding with loss-of-function of the enzyme phenylalanine hydroxylase (PAH) is the molecular basis of phenylketonuria in many individuals carrying missense mutations in the PAH gene. PAH is complexly regulated by its substrate L-Phenylalanine and its natural cofactor 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)). Sapropterin dihydrochloride, the synthetic form of BH(4), was recently approved as the first pharmacological chaperone to correct the loss-of-function phenotype. However, current knowledge about enzyme function and regulation in the therapeutic setting is scarce. This illustrates the need for comprehensive analyses of steady state kinetics and allostery beyond single residual enzyme activity determinations to retrace the structural impact of missense mutations on the phenylalanine hydroxylating system. Current standard PAH activity assays are either indirect (NADH) or discontinuous due to substrate and product separation before detection. We developed an automated fluorescence-based continuous real-time PAH activity assay that proved to be faster and more efficient but as precise and accurate as standard methods. Wild-type PAH kinetic analyses using the new assay revealed cooperativity of activated PAH toward BH(4), a previously unknown finding. Analyses of structurally preactivated variants substantiated BH(4)-dependent cooperativity of the activated enzyme that does not rely on the presence of l-Phenylalanine but is determined by activating conformational rearrangements. These findings may have implications for an individualized therapy, as they support the hypothesis that the patient's metabolic state has a more significant effect on the interplay of the drug and the conformation and function of the target protein than currently appreciated.

  14. 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

  15. Estimating the Universal Positions of Wireless Body Electrodes for Measuring Cardiac Electrical Activity.

    PubMed

    Tomasić, Ivan; Frljak, Sabina; Trobec, Roman

    2013-12-01

    A methodology is presented for estimating the wireless body electrode (WE) positions and for calculating the linear transformations that enable the synthesis of a 12-lead ECG or a multichannel ECG from three WEs, which in turn simplifies and improves the acquisition of ECGs. We present, compare, and evaluate three approaches to the synthesis: fully personalized, fully universal, and combined with universal leads and personalized transformations. The evaluation results show that WEs are an acceptable alternative to the standard 12-lead ECG device for patients with chronic myocardial ischemia, if either the fully personalized or combined approach is used. The median correlation coefficients are all higher than 0.94 and 0.92 for the fully personalized and combined approaches, respectively. The corresponding kappa and percentual diagnostic agreements between the synthesized and target 12-lead ECGs are 0.88 (95%) and 0.83 (92%), respectively. The evaluation additionally shows that the personalization of the transformations has more impact on the quality of the synthesized ECGs than the personalization of the WEs' positions.

  16. Relative spatial positions of tryptophan and cationic residues in helical membrane-active peptides determine their cytotoxicity.

    PubMed

    Rekdal, Øystein; Haug, Bengt Erik; Kalaaji, Manar; Hunter, Howard N; Lindin, Inger; Israelsson, Ingrid; Solstad, Terese; Yang, Nannan; Brandl, Martin; Mantzilas, Dimitrios; Vogel, Hans J

    2012-01-02

    The cytotoxic activity of 10 analogs of the idealized amphipathic helical 21-mer peptide (KAAKKAA)3, where three of the Ala residues at different positions have been replaced with Trp residues, has been investigated. The peptide's cytotoxic activity was found to be markedly dependent upon the position of the Trp residues within the hydrophobic sector of an idealized α-helix. The peptides with Trp residues located opposite the cationic sector displayed no antitumor activity, whereas those peptides with two or three Trp residues located adjacent to the cationic sector exhibited high cytotoxic activity when tested against three different cancer cell lines. Dye release experiments revealed that in contrast to the peptides with Trp residues located opposite the cationic sector, the peptides with Trp residues located adjacent to the cationic sector induced a strong permeabilizing activity from liposomes composed of a mixture of zwitterionic phosphatidylcholine and negatively charged phosphatidylserine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS)) (2:1) but not from liposomes composed of zwitterionic phosphatidylcholine, POPC. Fluorescence blue shift and quenching experiments revealed that Trp residues inserted deeper into the hydrophobic environment of POPC/POPS liposomes for peptides with high cytotoxic activity. Through circular dichroism studies, a correlation between the cytotoxic activity and the α-helical propensity was established. Structural studies of one inactive and two active peptides in the presence of micelles using NMR spectroscopy showed that only the active peptides adopted highly coiled to helical structures when bound to a membrane surface.

  17. ACTIVITY OF TRASTUZUMAB-EMTANSINE (TDM1) IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A CASE SERIES

    PubMed Central

    Keith, Kevin C.; Lee, Yueh; Ewend, Matthew G.; Zagar, Timothy M.; Anders, Carey K.

    2016-01-01

    The incidence of breast cancer brain metastasis (BCBM) is increasing due in part to improved management of systemic disease and prolonged survival. Despite this growing population of patients, there exists little consensus for the treatment of HER2-positive BCBM. Lapatinib, the only brain permeable targeted agent for HER2-positive cancer, has demonstrated limited intracranial response rates and little improvement in progression free survival (PFS) for HER-2 positive patients. Size constraints are believed to prevent larger monoclonal antibodies, such as pertuzumab and trastuzumab, from crossing the blood brain barrier (BBB). However, emerging evidence reveals that the BBB is perturbed in the setting of metastases, allowing for improved penetrance of these larger targeted agents. The disrupted BBB may allow for passage of ado-trastuzumab emtansine (TDM1), though little clinical information about its activity in BCBM patients is currently known. PMID:27114895

  18. 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,…

  19. The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis.

    PubMed

    Senis, Yotis A; Tomlinson, Michael G; Ellison, Stuart; Mazharian, Alexandra; Lim, Jenson; Zhao, Yan; Kornerup, Kristin N; Auger, Jocelyn M; Thomas, Steve G; Dhanjal, Tarvinder; Kalia, Neena; Zhu, Jing W; Weiss, Arthur; Watson, Steve P

    2009-05-14

    Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase-linked and G protein-coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein-coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.

  20. The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis

    PubMed Central

    Tomlinson, Michael G.; Ellison, Stuart; Mazharian, Alexandra; Lim, Jenson; Zhao, Yan; Kornerup, Kristin N.; Auger, Jocelyn M.; Thomas, Steve G.; Dhanjal, Tarvinder; Kalia, Neena; Zhu, Jing W.; Weiss, Arthur; Watson, Steve P.

    2009-01-01

    Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target. PMID:19246339

  1. 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…

  2. 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…

  3. 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…

  4. 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

  5. Effects of button position on a soft keyboard: Muscle activity, touch time, and discomfort in two-thumb text entry.

    PubMed

    Chang, Joonho; Choi, Bori; Tjolleng, Amir; Jung, Kihyo

    2017-04-01

    Intensive use of the thumbs for text entry on smartphones may contribute to discomfort, pain, or musculoskeletal disorders. This study investigated the effect of twenty-five button positions (5 rows × 5 columns) on a soft keyboard for two-thumb entry. Two experiments measured muscle activity, touch time, and discomfort as a function of the button positions. In Phase I, the muscle activities of two intrinsic (abductor pollicis brevis and first dorsal interossei) and two extrinsic (abductor pollicis longus and extensor digitorum communis) muscles associated with thumb motions were observed for ten college students (age: 24.2). In Phase II, touch time and discomfort were measured for 40 college students (age: 23.6). The results demonstrated that the %MVCs of the intrinsic muscles significantly increased when the thumbs flexed and abducted. Also, the button positions near the rest positions of the thumbs resulted in significantly shorter touch times (0.66 s) and lower discomfort ratings (0.70 pt) than their peripheral buttons (0.76 s; 2.29 pt).

  6. 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.

  7. Position but not color deviants result in visual mismatch negativity in an active oddball task.

    PubMed

    Berti, Stefan

    2009-05-06

    Changes in the visual environment might be detected automatically. This function is provided by the sensory systems and showed, for instance, by the pop-out phenomenon. Automatic change detection is also observable within visual oddball paradigms, where rare changes are introduced in an irrelevant stimulus feature; the detection of deviant stimuli is accompanied by a negative component (so-called visual mismatch negativity) in the human event-related brain potential. In this study, the deviating stimulus feature was embedded in a task-relevant object presented in the focus of attention. With this, visual mismatch negativity was observable only with position deviants presented in the upper visual half field but not by lower half field presentation or color deviants.

  8. Isolation of highly active monoclonal antibodies against multiresistant gram-positive bacteria.

    PubMed

    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.

  9. 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

  10. 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.

  11. Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

    PubMed

    Lin, Du'an; Lam, Hiu Yung; Han, Wenbo; Cotroneo, Nicole; Pandya, Bhaumik A; Li, Xuechen

    2017-02-01

    Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported.

  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. 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

  14. Positive effect of dietary lutein and cholesterol on the undirected song activity of an opportunistic breeder

    PubMed Central

    Pinxten, Rianne; Zaid, Erika; Eens, Marcel

    2016-01-01

    Song is a sexually selected trait that is thought to be an honest signal of the health condition of an individual in many bird species. For species that breed opportunistically, the quantity of food may be a determinant of singing activity. However, it is not yet known whether the quality of food plays an important role in this respect. The aim of the present study was to experimentally investigate the role of two calorie-free nutrients (lutein and cholesterol) in determining the expression of a sexually selected behavior (song rate) and other behaviors (locomotor activity, self-maintenance activity, eating and resting) in male zebra finches (Taeniopygia guttata). We predicted that males supplemented with lutein and cholesterol would sing at higher rates than controls because both lutein and cholesterol have important health-related physiological functions in birds and birdsong mirrors individual condition. To control for testosterone secretion that may upregulate birdsong, birds were exposed to a decreasing photoperiod. Our results showed that control males down-regulated testosterone in response to a decreasing photoperiod, while birds treated with lutein or cholesterol maintained a constant singing activity. Both lutein- and cholesterol-supplemented groups sang more than control groups by the end of the experiment, indicating that the quality of food can affect undirected song irrespective of circulating testosterone concentrations. None of the other measured behaviors were affected by the treatment, suggesting that, when individuals have full availability of food, sexually selected song traits are more sensitive to the effect of food quality than other behavioral traits. Overall the results support our prediction that undirected song produced by male zebra finches signals access to high-quality food. PMID:27761321

  15. Peripherally injected CCK-8S activates CART positive neurons of the paraventricular nucleus in rats

    PubMed Central

    Noetzel, Steffen; Inhoff, Tobias; Goebel, Miriam; Taché, Yvette; Veh, Rüdiger W.; Bannert, Norbert; Grötzinger, Carsten; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

    2014-01-01

    Cholecystokinin (CCK) plays a role in the short-term inhibition of food intake. Cocaine- and amphetamine-regulated transcript (CART) peptide has been observed in neurons of the paraventricular nucleus (PVN). It has been reported that intracerebroventricular injection of CART peptide inhibits food intake in rodents. The aim of the study was to determine whether intraperitoneally (ip) injected CCK-8S affects neuronal activity of PVN-CART neurons. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15 M NaCl ip (n = 4/group). The number of c-Fos-immunoreactive neurons was determined in the PVN, arcuate nucleus (ARC), and the nucleus of the solitary tract (NTS). CCK-8S dose-dependently increased the number of c-Fos-immunoreactive neurons in the PVN (mean ± SEM: 102 ± 6 vs. 150 ± 5 neurons/section, p < 0.05) and compared to vehicle treated rats (18 ± 7, p < 0.05 vs. 6 and 10 μg/kg CCK-8S). CCK-8S at both doses induced an increase in the number of c-Fos-immunoreactive neurons in the NTS (65 ± 13, p < 0.05, and 182 ± 16, p < 0.05). No effect on the number of c-Fos neurons was observed in the ARC. Immunostaining for CART and c-Fos revealed a dose-dependent increase of activated CART neurons (19 ± 3 vs. 29 ± 7; p < 0.05), only few activated CART neuron were observed in the vehicle group (1 ± 0). The present observation shows that CCK-8S injected ip induces an increase in neuronal activity in PVN-CART neurons and suggests that CART neurons in the PVN may play a role in the mediation of peripheral CCK-8S's anorexigenic effects. PMID:20307613

  16. Rewiring mitogen-activated protein kinase cascade by positive feedback confers potato blight resistance.

    PubMed

    Yamamizo, Chihiro; Kuchimura, Kazuo; Kobayashi, Akira; Katou, Shinpei; Kawakita, Kazuhito; Jones, Jonathan D G; Doke, Noriyuki; Yoshioka, Hirofumi

    2006-02-01

    Late blight, caused by the notorious pathogen Phytophthora infestans, is a devastating disease of potato (Solanum tuberosum) and tomato (Solanum lycopersicum), and during the 1840s caused the Irish potato famine and over one million fatalities. Currently, grown potato cultivars lack adequate blight tolerance. Earlier cultivars bred for resistance used disease resistance genes that confer immunity only to some strains of the pathogen harboring corresponding avirulence gene. Specific resistance gene-mediated immunity and chemical controls are rapidly overcome in the field when new pathogen races arise through mutation, recombination, or migration from elsewhere. A mitogen-activated protein kinase (MAPK) cascade plays a pivotal role in plant innate immunity. Here we show that the transgenic potato plants that carry a constitutively active form of MAPK kinase driven by a pathogen-inducible promoter of potato showed high resistance to early blight pathogen Alternaria solani as well as P. infestans. The pathogen attack provoked defense-related MAPK activation followed by induction of NADPH oxidase gene expression, which is implicated in reactive oxygen species production, and resulted in hypersensitive response-like phenotype. We propose that enhancing disease resistance through altered regulation of plant defense mechanisms should be more durable and publicly acceptable than engineering overexpression of antimicrobial proteins.

  17. Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling.

    PubMed

    Lu, Li; Rao, Li; Jia, Huanhuan; Chen, Jun; Lu, Xingyan; Yang, Guozhu; Li, Qingnan; Lee, Kenneth Ka Ho; Yang, Li

    2017-02-03

    Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose-dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up-regulation of downstream osteoclast-related target genes expression. The baicalin-induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p-ERK (U0126) and the Mitf-specific siRNA, respectively. Protein-ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p-ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p-ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.

  18. Nitrogen positional scanning in tetramines active against HIV-1 as potential CXCR4 inhibitors.

    PubMed

    Puig de la Bellacasa, Raimon; Gibert, Albert; Planesas, Jesús M; Ros-Blanco, Laia; Batllori, Xavier; Badía, Roger; Clotet, Bonaventura; Esté, José; Teixidó, Jordi; Borrell, José I

    2016-01-28

    The paradigm, derived from bicyclams and other cyclams, by which it is necessary to use the p-phenylene moiety as the central core in order to achieve high HIV-1 antiviral activities has been reexamined for the more flexible and less bulky structures 4, previously described by our group as potent HIV-1 inhibitors. The symmetrical compounds 7{x,x} and the non-symmetrical compounds 8{x,y} were designed, synthesized and biologically evaluated in order to explore the impact on the biological activity of the distance between the phenyl ring and the first nitrogen atom of the side chains. EC50 exactly followed the order 7{x,x} < 8{x,x} < 4{x,x} indicating that, for such flexible tetramines, the presence of two methylene units on each side of the central phenyl ring increases the biological activity contrary to AMD3100. A computational study of the interactions of 4{3,3}, 7{3,3} and 8{3,3} with CXCR4 revealed interactions in the same pocket region with similar binding modes for 4{3,3} and 7{3,3} but a different one for 8{3,3}.

  19. Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

    PubMed

    Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

    2015-11-12

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

  20. Achievement of the POSITIVE (Participation-Oriented Safety Improvement by Trade Union InitiatiVE) activities in the Philippines.

    PubMed

    Tachi, Norihide; Itani, Toru; Takeyama, Hidemaro; Yoshikawa, Toru; Suzuki, Koji; Castro, Ariel B

    2006-01-01

    The POSITIVE (Participation-oriented safety improvement by trade union initiative) programme was introduced into the Philippines in 1995. The monitoring of activities was carried out in 2004 among core trainers who had been trained before. The results of the questionnaire survey showed that the core trainers evaluated their activities satisfactory in general, and particularly the training activities were considered excellent. Also, the union workers who had been trained by the POSITIVE programme implemented improvements at the rate of around 5 examples a year on average. It was of note that the installation ratio (the number of installations/that of plans) was higher in small- and medium-sized enterprises than in larger companies, although the numbers of plans and installations of improvements were greater in large enterprises. Together with the previous findings, the present results suggest that the POSITIVE-style participatory training program is effective and efficient for workers to take actions for the OSH in not only larger enterprises but also small enterprises.

  1. Constitutively expressed COX-2 in osteoblasts positively regulates Akt signal transduction via suppression of PTEN activity.

    PubMed

    Li, Ching-Ju; Chang, Je-Ken; Wang, Gwo-Jaw; Ho, Mei-Ling

    2011-02-01

    Cyclooxygenase-2 (COX-2) is thought to be an inducible enzyme, but increasing reports indicate that COX-2 is constitutively expressed in several organs. The status of COX-2 expression in bone and its physiological role remains undefined. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, which commonly suppress COX-2 activity, were reported to suppress osteoblast proliferation via Akt/FOXO3a/p27(Kip1) signaling, suggesting that COX-2 may be the key factor of the suppressive effects of NSAIDs on proliferation. Although Akt activation correlates with PTEN deficiency and cell viability, the role of COX-2 on PTEN/Akt regulation remains unclear. In this study, we hypothesized that COX-2 may be constitutively expressed in osteoblasts and regulate PTEN/Akt-related proliferation. We examined the localization and co-expression of COX-2 and p-Akt in normal mouse femurs and in cultured mouse (mOBs) and human osteoblasts (hOBs). Our results showed that osteoblasts adjacent to the trabeculae, periosteum and endosteum in mouse femurs constitutively expressed COX-2, while COX-2 co-expressed with p-Akt in osteoblasts sitting adjacent to trabeculae in vivo, and in mOBs and hOBs in vitro. We further used COX-2 siRNA to test the role of COX-2 in Akt signaling in hOBs; COX-2 silencing significantly inhibited PTEN phosphorylation, enhanced PTEN activity, and suppressed p-Akt level and proliferation. However, replenishment of the COX-2 enzymatic product, PGE2, failed to reverse COX-2-dependent Akt phosphorylation. Furthermore, transfection with recombinant human COX-2 (rhCOX-2) significantly reversed COX-2 siRNA-suppressed PTEN phosphorylation, but this effect was reduced when the enzymatic activity of rhCOX-2 was blocked. This finding indicated that the effect of COX-2 on PTEN/Akt signaling is not related to PGE2 but still dependent on COX-2 enzymatic activity. Conversely, COX-1 silencing did not affect PTEN/Akt signaling. Our findings provide

  2. 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.

  3. 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.

  4. 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

  5. Recruitment of calcineurin to the TCR positively regulates T cell activation.

    PubMed

    Dutta, Debjani; Barr, Valarie A; Akpan, Itoro; Mittelstadt, Paul R; Singha, Laishram I; Samelson, Lawrence E; Ashwell, Jonathan D

    2017-02-01

    Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant). Notably, CsA inhibited integrin-LFA-1-dependent and NFAT-independent adhesion of T cells to the intercellular adhesion molecule ICAM-1, with little effect on cells expressing mutant Lck. These results provide new understanding of how widely used immunosuppressive drugs interfere with essential processes in the immune response.

  6. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways.

    PubMed

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

    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-Jkappa-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.

  7. 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.

  8. 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

  9. 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.

  10. Putamen Activation Represents an Intrinsic Positive Prediction Error Signal for Visual Search in Repeated Configurations.

    PubMed

    Sommer, Susanne; Pollmann, Stefan

    2016-01-01

    We investigated fMRI responses to visual search targets appearing at locations that were predicted by the search context. Based on previous work in visual category learning we expected an intrinsic reward prediction error signal in the putamen whenever the target appeared at a location that was predicted with some degree of uncertainty. Comparing target appearance at locations predicted with 50% probability to either locations predicted with 100% probability or unpredicted locations, increased activation was observed in left posterior putamen and adjacent left posterior insula. Thus, our hypothesis of an intrinsic prediction error-like signal was confirmed. This extends the observation of intrinsic prediction error-like signals, driven by intrinsic rather than extrinsic reward, to memory-driven visual search.

  11. Putamen Activation Represents an Intrinsic Positive Prediction Error Signal for Visual Search in Repeated Configurations

    PubMed Central

    Sommer, Susanne; Pollmann, Stefan

    2016-01-01

    We investigated fMRI responses to visual search targets appearing at locations that were predicted by the search context. Based on previous work in visual category learning we expected an intrinsic reward prediction error signal in the putamen whenever the target appeared at a location that was predicted with some degree of uncertainty. Comparing target appearance at locations predicted with 50% probability to either locations predicted with 100% probability or unpredicted locations, increased activation was observed in left posterior putamen and adjacent left posterior insula. Thus, our hypothesis of an intrinsic prediction error-like signal was confirmed. This extends the observation of intrinsic prediction error-like signals, driven by intrinsic rather than extrinsic reward, to memory-driven visual search. PMID:27867436

  12. Active learning in a neuroethics course positively impacts moral judgment development in undergraduates.

    PubMed

    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.

  13. 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

  14. Pellino protein from pacific white shrimp Litopenaeus vannamei positively regulates NF-κB activation.

    PubMed

    Li, Chaozheng; Chai, Jiaoting; Li, Haoyang; Zuo, Hongliang; Wang, Sheng; Qiu, Wei; Weng, Shaoping; He, Jianguo; Xu, Xiaopeng

    2014-06-01

    Pellino, named after its property that binds Pelle (the Drosophila melanogaster homolog of IRAK1), is a highly conserved E3 class ubiquitin ligase in both vertebrates and invertebrates. Pellino interacts with phosphorylated IRAK1, causing polyubiquitination of IRAK1, and plays a critical upstream role in the toll-like receptor (TLR) pathway. In this study, we firstly cloned and identified a crustacean Pellino from pacific white shrimp Litopenaeus vannamei (LvPellino). LvPellino contains a putative N-terminal forkhead-associated (FHA) domain and a C-terminal ring finger (RING) domain with a potential E3 ubiquitin-protein ligase activity, and shows a high similarity with D. melanogaster Pellino. LvPellino could interact with L. vannamei Pelle (LvPelle) and over-expression of LvPellino could increase the activity of LvDorsal (a L. vannamei homolog of NF-κB) on promoters containing NF-κB binding motifs and enhance the expression of arthropod antimicrobial peptides (AMPs). The LvPellino protein was located in the cytoplasm and nucleus and LvPellino mRNA was detected in all the tissues examined and could be up-regulated after lipopolysaccharides, white spot syndrome virus (WSSV), Vibrio parahaemolyticus, and Staphylococcus aureus challenges, suggesting a stimulation response of LvPellino to bacterial and immune stimulant challenges. Knockdown of LvPellino in vivo could significantly decrease the expression of AMPs and increase the mortality of shrimps caused by V. parahaemolyticus challenge. However, suppression of the LvPellino expression could not change the mortality caused by WSSV infection, and dual-luciferase reporter assays demonstrated that over-expression of LvPellino could enhance the promoters of WSSV genes wsv069 (ie1), wsv303, and wsv371, indicating a complex role of LvPellino in WSSV pathogenesis and shrimp antiviral mechanisms.

  15. Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia

    PubMed Central

    Mandali, Alekhya; Chakravarthy, V. Srinivasa

    2016-01-01

    Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic

  16. Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia.

    PubMed

    Mandali, Alekhya; Chakravarthy, V Srinivasa

    2016-01-01

    Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic

  17. Highly active modulators of indole signaling alter pathogenic behaviors in Gram-negative and Gram-positive bacteria.

    PubMed

    Minvielle, Marine J; Eguren, Kristen; Melander, Christian

    2013-12-16

    Indole is a universal signal that regulates various bacterial behaviors, such as biofilm formation and antibiotic resistance. To generate mechanistic probes of indole signaling and control indole-mediated pathogenic phenotypes in both Gram-positive and Gram-negative bacteria, we have investigated the use of desformylflustrabromine (dFBr) derivatives to generate highly active indole mimetics. We have developed non-microbicidal dFBr derivatives that are 27-2000 times more active than indole in modulating biofilm formation, motility, acid resistance, and antibiotic resistance. The activity of these analogues parallels indole, because they are dependent on temperature, the enzyme tryptophanase TnaA, and the transcriptional regulator SdiA. This investigation demonstrates that molecules based on the dFBr scaffold can alter pathogenic behaviors by mimicking indole-signaling pathways.

  18. Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms.

    PubMed

    Blondeau, J M; Laskowski, R; Bjarnason, J; Stewart, C

    2000-02-01

    Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.

  19. 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

  20. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness.

    PubMed

    Hogarth, Luke W; Burkett, Brendan J; McKean, Mark R

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson's correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03-1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69-1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43-0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions.

  1. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    PubMed Central

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson’s correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03–1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69–1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43–0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions. PMID:26642320

  2. 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.

  3. Detection of (Leu-7)-positive cells with NK activity in human gingival tissues from patients with periodontitis

    SciTech Connect

    Komiyama, K.; Hirsch, H.Z.; Mestecky, J.; Moro, I.

    1986-03-05

    Natural killer (NK) cells have been identified in peripheral blood, lymphoid tissue and more recently in gut mucosa and may be involved in the regulation of immunoglobulin synthesis. They have assayed gingival tissues obtained from 25 periodontitis patients, for the presence and activity of NK cells. Routine histological techniques demonstrated an inflammatory infiltrate dominated by plasma cells and B lymphocytes. Indirect staining procedures with a biotin-labeled mouse anti-human, Leu-7 antibody revealed the presence of numerous positive cells accompanying the inflammatory cellular infiltrate in perivascular areas. Several specimens demonstrated positive-staining cells in the epithelium as well. Few cells were observed in histologically uninflammed areas. Single cell suspension obtained by collagenase digestion of 5 gingival samples were used in /sup 51/Cr release cytotoxicity assay against K562 cells. Three of the five samples were positive in this assay. The finding of Leu-7-positive cells in areas of intense plasma cell foci but not in uninflammed areas, may support a role for these cells in the regulation of immunoglobulin synthesis in oral mucosal tissues.

  4. 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.

  5. 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.

  6. 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

  7. Co-operative leukemogenesis in acute myeloid leukemia and acute promyelocytic leukemia reveals C/EBPα as a common target of TRIB1 and PML/RARA

    PubMed Central

    Keeshan, Karen; Vieugué, Pauline; Chaudhury, Shahzya; Rishi, Loveena; Gaillard, Coline; Liang, Lu; Garcia, Elaine; Nakamura, Takuro; Omidvar, Nader; Kogan, Scott C.

    2016-01-01

    The PML/RARA fusion protein occurs as a result of the t(15;17) translocation in the acute promyelocytic leukemia subtype of human acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia, including acute promyelocytic leukemia. We previously demonstrated that gain of chromosome 8-containing MYC is of central importance in trisomy 8, but the role of the nearby TRIB1 gene has not been experimentally addressed in this context. We have now tested the hypothesis that both MYC and TRIB1 have functional roles underlying leukemogenesis of trisomy 8 by using retroviral vectors to express MYC and TRIB1 in wild-type bone marrow and in marrow that expressed a PML/RARA transgene. Interestingly, although MYC and TRIB1 readily co-operated in leukemogenesis for wild-type bone marrow, TRIB1 provided no selective advantage to cells expressing PML/RARA. We hypothesized that this lack of co-operation between PML/RARA and TRIB1 reflected a common pathway for their effect: both proteins targeting the myeloid transcription factor C/EBPα. In support of this idea, TRIB1 expression abrogated the all-trans retinoic acid response of acute promyelocytic leukemia cells in vitro and in vivo. Our data delineate the common and redundant inhibitory effects of TRIB1 and PML/RARA on C/EBPα providing a potential explanation for the lack of selection of TRIB1 in human acute promyelocytic leukemia, and highlighting the key role of C/EBPs in acute promyelocytic leukemia pathogenesis and therapeutic response. In addition, the co-operativity we observed between MYC and TRIB1 in the absence of PML/RARA show that, outside of acute promyelocytic leukemia, gain of both genes may drive selection for trisomy 8. PMID:27390356

  8. Active infective endocarditis due to Erysipelothrix rhusiopathiae: zoonosis caused by vancomycin-resistant gram-positive rod.

    PubMed

    Miura, Takashi; Hashizume, Koji; Ariyoshi, Tsuneo; Miwa, Takashi; Furumoto, Akitsugu; Izumida, Mai; Yanagihara, Katsunori; Eishi, Kiyoyuki

    2013-02-01

    A 42-year-old female who was a voluntary worker in a school for handicapped children was referred to us for surgery for active infective endocarditis. Trans-esophageal echocardiography showed 2 large mobile vegetations on the aortic valve and severe aortic regurgitation. Aortic valve replacement was performed to prevent septic embolism and deterioration of congestive heart failure. The empiric therapy with vancomycin, ampicillin, and gentamycin was initiated because a pathogen was not identified. But Erysipelothrix rhusiopathiae (gram-positive rod) was isolated on the 4th day after surgery. The target therapy with penicillin G and clindamycin was started and continued for 4 weeks after surgery. The inflammatory parameters improved steadily and the patient was discharged on the 36th day after surgery. Infective endocarditis due to gram-positive rods can be easily mistaken for streptococci or dismissed as a skin contamination. But, E. rhusiopathiae endocarditis should be considered in the differential diagnosis.

  9. Structure-activity relationships of 4-position diamine quinoline methanols as intermittent preventative treatment (IPT) against Plasmodium falciparum.

    PubMed

    Milner, Erin; Gardner, Sean; Moon, Jay; Grauer, Kristina; Auschwitz, Jennifer; Bathurst, Ian; Caridha, Diana; Gerena, Lucia; Gettayacamin, Montip; Johnson, Jacob; Kozar, Michael; Lee, Patricia; Leed, Susan; Li, Qigui; McCalmont, William; Melendez, Victor; Roncal, Norma; Sciotti, Richard; Smith, Bryan; Sousa, Jason; Tungtaeng, Anchalee; Wipf, Peter; Dow, Geoffrey

    2011-09-22

    A library of diamine quinoline methanols were designed based on the mefloquine scaffold. The systematic variation of the 4-position amino alcohol side chain led to analogues that maintained potency while reducing accumulation in the central nervous system (CNS). Although the mechanism of action remains elusive, these data indicate that the 4-position side chain is critical for activity and that potency (as measured by IC(90)) does not correlate with accumulation in the CNS. A new lead compound, (S)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(2-(cyclopropylamino)ethylamino)ethanol (WR621308), was identified with single dose efficacy and substantially lower permeability across MDCK cell monolayers than mefloquine. This compound could be appropriate for intermittent preventative treatment (IPTx) indications or other malaria treatments currently approved for mefloquine.

  10. 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.

  11. Modeling the impact of spinal cord stimulation paddle lead position on impedance, stimulation threshold, and activation region.

    PubMed

    Xiaoyi Min; Kent, Alexander R

    2015-08-01

    The effectiveness of spinal cord stimulation (SCS) for chronic pain treatment depends on selection of appropriate stimulation settings, which can be especially challenging following posture change or SCS lead migration. The objective of this work was to investigate the feasibility of using SCS lead impedance for determining the location of a SCS lead and for detecting lead migration, as well as the impact of axial movement and rotation of the St. Jude Medical PENTA™ paddle in the dorsal-ventral or medial-lateral directions on dorsal column (DC) stimulation thresholds and neural activation regions. We used a two-stage computational model, including a finite element method model of field potentials in the spinal cord during stimulation, coupled to a biophysical cable model of mammalian, myelinated nerve fibers to calculate tissue impedance and nerve fiber activation within the DC. We found that SCS lead impedance was highly sensitive to the distance between the lead and cerebrospinal fluid (CSF) layer. In addition, among all the lead positions studied, medial-lateral movement resulted in the most substantial changes to SC activation regions. These results suggest that impedance can be used for detecting paddle position and lead migration, and therefore for guiding SCS programming.

  12. 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

  13. Structure activity studies of nociceptin/orphanin FQ(1-13)-NH2 derivatives modified in position 5.

    PubMed

    Guerrini, Remo; Marzola, Erika; Trapella, Claudio; Pacifico, Salvatore; Cerlesi, Maria Camilla; Malfacini, Davide; Ferrari, Federica; Bird, Mark Francis; Lambert, David George; Salvadori, Severo; Calo, Girolamo

    2015-04-01

    Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide acting as the endogenous ligand of the N/OFQ peptide receptor (NOP). N/OFQ(1-13)-NH2 is the shortest N/OFQ sequence maintaining the same potency and efficacy as the natural peptide. Thus N/OFQ(1-13)-NH2 was used as chemical template for investigating the structure activity relationship of threonine in position 5. 28 [X(5)]N/OFQ(1-13)-NH2 derivatives, in which Thr was substituted with natural and unnatural residues, were synthesized and characterized pharmacologically for their effects at the human NOP receptor. Two different functional assays were used: agonist stimulated [(35)S]GTPγS binding in cell membranes and calcium mobilization in whole cells co-expressing chimeric G proteins. All [X(5)]N/OFQ(1-13)-NH2 derivatives behaved as full NOP agonists showing large differences in their potency. There was an excellent correlation between the results obtained in the two assays. The results of this study suggest that: position 5 does not play a pivotal role in receptor activation; the secondary alcoholic function of Thr is not important for receptor binding; side chain size, lipo/hydrophilic balance as well as hydrogen bond capability are also not crucial for receptor binding; an aliphatic amino function positively charged with at least 3 carbon atom distance from the peptide backbone has a huge disrupting effect on receptor binding. In conclusion this study demonstrates that a simple ethyl side chain as in compound 23 is sufficient in N/OFQ position 5 for maintaining bioactivity.

  14. Computational analysis of negative and positive allosteric modulator binding and function in metabotropic glutamate receptor 5 (in)activation.

    PubMed

    Dalton, James A R; Gómez-Santacana, Xavier; Llebaria, Amadeu; Giraldo, Jesús

    2014-05-27

    Metabotropic glutamate receptors (mGluRs) are high-profile G-protein coupled receptors drug targets because of their involvement in several neurological disease states, and mGluR5 in particular is a subtype whose controlled allosteric modulation, both positive and negative, can potentially be useful for the treatment of schizophrenia and relief of chronic pain, respectively. Here we model mGluR5 with a collection of positive and negative allosteric modulators (PAMs and NAMs) in both active and inactive receptor states, in a manner that is consistent with experimental information, using a specialized protocol that includes homology to increase docking accuracy, and receptor relaxation to generate an individual induced fit with each allosteric modulator. Results implicate two residues in particular for NAM and PAM function: NAM interaction with W785 for receptor inactivation, and NAM/PAM H-bonding with S809 for receptor (in)activation. Models suggest the orientation of the H-bond between allosteric modulator and S809, controlled by PAM/NAM chemistry, influences the position of TM7, which in turn influences the shape of the allosteric site, and potentially the receptor state. NAM-bound and PAM-bound mGluR5 models also reveal that although PAMs and NAMs bind in the same pocket and share similar binding modes, they have distinct effects on the conformation of the receptor. Our models, together with the identification of a possible activation mechanism, may be useful in the rational design of new allosteric modulators for mGluR5.

  15. 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.

  16. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome.

    PubMed

    Juneja, Deven; Mohan, S; Veturi, Vivek V; Gopal, Palepu B

    2009-01-01

    Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC) and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  17. 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…

  18. 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.

  19. Selective Activation Around the Left Occipito-Temporal Sulcus for Words Relative to Pictures: Individual Variability or False Positives?

    PubMed Central

    Wright, Nicholas D; Mechelli, Andrea; Noppeney, Uta; Veltman, Dick J; Rombouts, Serge ARB; Glensman, Janice; Haynes, John-Dylan; Price, Cathy J

    2008-01-01

    We used high-resolution fMRI to investigate claims that learning to read results in greater left occipito-temporal (OT) activation for written words relative to pictures of objects. In the first experiment, 9/16 subjects performing a one-back task showed activation in ≥1 left OT voxel for words relative to pictures (P < 0.05 uncorrected). In a second experiment, another 9/15 subjects performing a semantic decision task activated ≥1 left OT voxel for words relative to pictures. However, at this low statistical threshold false positives need to be excluded. The semantic decision paradigm was therefore repeated, within subject, in two different scanners (1.5 and 3 T). Both scanners consistently localised left OT activation for words relative to fixation and pictures relative to words, but there were no consistent effects for words relative to pictures. Finally, in a third experiment, we minimised the voxel size (1.5 × 1.5 × 1.5 mm3) and demonstrated a striking concordance between the voxels activated for words and pictures, irrespective of task (naming vs. one-back) or script (English vs. Hebrew). In summary, although we detected differential activation for words relative to pictures, these effects: (i) do not withstand statistical rigour; (ii) do not replicate within or between subjects; and (iii) are observed in voxels that also respond to pictures of objects. Our findings have implications for the role of left OT activation during reading. More generally, they show that studies using low statistical thresholds in single subject analyses should correct the statistical threshold for the number of comparisons made or replicate effects within subject. Hum Brain Mapp 2008. © 2007 Wiley-Liss, Inc. PMID:17712786

  20. Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels

    PubMed Central

    Hougaard, C; Eriksen, B L; Jørgensen, S; Johansen, T H; Dyhring, T; Madsen, L S; Strøbæk, D; Christophersen, P

    2007-01-01

    Background and purpose: Positive modulators of small conductance Ca2+-activated K+ channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1-EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca2+-activated K+ channel (IK). This paper demonstrates, for the first time, subtype-selective positive modulation of SK channels. Experimental approach: Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) on recombinant hSK1-3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells. Key results: CyPPA was found to be a positive modulator of hSK3 (EC50 = 5.6 ± 1.6 μM, efficacy 90 ± 1.8 %) and hSK2 (EC50 = 14 ± 4 μM, efficacy 71 ± 1.8 %) when measured in inside-out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration-dependent increase in the apparent Ca2+-sensitivity of channel activation, changing the EC50(Ca2+) from 429 nM to 59 nM. Conclusions and implications: As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1-EBIO and NS309 to distinguish SK3/SK2- from SK1/IK-mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co-express in certain peripheral tissues. PMID:17486140

  1. Motor neuron cell bodies are actively positioned by Slit/Robo repulsion and Netrin/DCC attraction.

    PubMed

    Kim, Minkyung; Fontelonga, Tatiana; Roesener, Andrew P; Lee, Haeram; Gurung, Suman; Mendonca, Philipe R F; Mastick, Grant S

    2015-03-01

    Motor neurons differentiate from a ventral column of progenitors and settle in static clusters, the motor nuclei, next to the floor plate. Within these cell clusters, motor neurons receive afferent input and project their axons out to muscle targets. The molecular mechanisms that position motor neurons in the neural tube remain poorly understood. The floor plate produces several types of guidance cues with well-known roles in attracting and repelling axons, including the Slit family of chemorepellents via their Robo receptors, and Netrin1 via its DCC attractive receptor. In the present study we found that Islet1(+) motor neuron cell bodies invaded the floor plate of Robo1/2 double mutant mouse embryos or Slit1/2/3 triple mutants. Misplaced neurons were born in their normal progenitor column, but then migrated tangentially into the ventral midline. Robo1 and 2 receptor expression in motor neurons was confirmed by reporter gene staining and anti-Robo antibody labeling. Mis-positioned motor neurons projected their axons longitudinally within the floor plate, and failed to reach their normal exit points. To test for potential counteracting ventral attractive signals, we examined Netrin-1 and DCC mutants, and found that motor neurons shifted dorsally in the hindbrain and spinal cord, suggesting that Netrin-1/DCC signaling normally attracts motor neurons closer to the floor plate. Our results show that motor neurons are actively migrating cells, and are normally trapped in a static position by Slit/Robo repulsion and Netrin-1/DCC attraction.

  2. Glucocorticoid--receptor interactions. Studies of the negative co-operativity induced by steroid interactions with a secondary, hydrophobic, binding site.

    PubMed Central

    Jones, T R; Bell, P A

    1980-01-01

    The effects of steroids on the binding of [1,2-3H]dexamethasone and [1,2-3H]progesterone to the glucocorticoid receptor of rat thymus cytosol were studied. Although both glucocorticoid agonists and antagonists competed with [1,2-3H]dexamethasone for binding to the receptor under equilibrium conditions, only glucocorticoid antagonists of partial agonists, at micromolar concentrations, were capable of accelerating the rate of dissociation of previously bound [1,2-3H]dexamethasone from the receptor. Antagonists or partial agonists also enhanced the rate of dissociation of [1,2-3H]progesterone from the glucocorticoid receptor, with identical specificity and concentration--response characteristics. These effects are attributed to the presence on the receptor of a secondary, low-affinity, binding site for glucocorticoid antagonists, the occupancy of which produces negatively co-operative interactions with the primary glucocorticoid-binding site. In contrast with the interactions with the primary site, the interactions of steroids with the negatively co-operative site appear to be primarily hydrophobic in nature, and the site resembles the steroid-binding site of progestin-binding proteins in its specificity, though not its affinity. The results also suggest that the initial interactions of both glucocorticoid agonists and antagonists with the receptor under equilibrium conditions are with one primary site on a receptor existing in one conformation only. PMID:7406882

  3. Biphalin analogs containing β(3)-homo-amino acids at the 4,4' positions: Synthesis and opioid activity profiles.

    PubMed

    Frączak, Oliwia; Lasota, Anika; Kosson, Piotr; Leśniak, Anna; Muchowska, Adriana; Lipkowski, Andrzej W; Olma, Aleksandra

    2015-04-01

    Biphalin, a synthetic opioid octapeptide with a palindromic sequence has high analgesic activity. Biphalin displays a strong affinity for μ and δ-opioid receptors, and a significant to κ-receptor. The paper reports the synthesis of novel analogs of biphalin containing β(3)-homo-amino acid residues at the 4,4' positions and a hydrazine or 1,2-phenylenediamine linker. The potency and selectivity of the peptides were evaluated by a competitive receptor-binding assay in rat brain homogenate using [(3)H]DAMGO (a μ ligand) and [(3)H]DELT (a δ ligand). Analogs with β(3)-h-p-NO2Phe in positions 4 and 4' are the most active compounds. Selectivity depends on the degree of freedom between the two pharmacophore moieties. Analogs with a hydrazine linker show noticeable binding selectivity to μ receptors (IC50(μ)=0.72nM; IC50(δ)=4.66nM), while the peptides with a 1,2-phenylenediamine linker show slight δ selectivity (IC50(μ)=10.97nM; IC50(δ)=1.99nM). Tyr-d-Ala-Gly-β(3)-h-p-NO2PheNHNH-β(3)-h-p-NO2Phe (1) and (Tyr-d-Ala-Gly-β(3)-h-p-NO2PheNH)2 (2) produced greater antinociceptive effect compared to morphine after i.t. administration.

  4. Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

    PubMed Central

    Fedrigo, Olivier; Babbitt, Courtney C.; Wortham, Matthew; Tewari, Alok K.; London, Darin; Song, Lingyun; Lee, Bum-Kyu; Iyer, Vishwanath R.; Parker, Stephen C. J.; Margulies, Elliott H.; Wray, Gregory A.; Furey, Terrence S.; Crawford, Gregory E.

    2012-01-01

    Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species. PMID:22761590

  5. Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis

    PubMed Central

    Park, Joon Hyeong; Seo, Yu Mi; Han, Seung Beom; Kim, Ki Hwan; Rhim, Jung Woo; Chung, Nack Gyun; Kim, Myung Shin; Kang, Jin Han

    2016-01-01

    Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded. PMID:27826329

  6. Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems.

    PubMed

    Benedetti, Fabrizio; Thoen, Wilma; Blanchard, Catherine; Vighetti, Sergio; Arduino, Claudia

    2013-03-01

    Pain is a negative emotional experience that is modulated by a variety of psychological factors through different inhibitory systems. For example, endogenous opioids and cannabinoids have been found to be involved in stress and placebo analgesia. Here we show that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. We induced ischemic arm pain in healthy volunteers, who had to tolerate the pain as long as possible. One group was informed about the aversive nature of the task, as done in any pain study. Conversely, a second group was told that the ischemia would be beneficial to the muscles, thus emphasizing the usefulness of the pain endurance task. We found that in the second group pain tolerance was significantly higher compared to the first one, and that this effect was partially blocked by the opioid antagonist naltrexone alone and by the cannabinoid antagonist rimonabant alone. However, the combined administration of naltrexone and rimonabant antagonized the increased tolerance completely. Our results indicate that a positive approach to pain reduces the global pain experience through the co-activation of the opioid and cannabinoid systems. These findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral and/or pharmacological manipulation of the meaning of pain can represent an effective approach to pain management.

  7. 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

  8. 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

  9. Antimicrobial Activities of Leaf Extracts of Guava (Psidium guajava L.) on Two Gram-Negative and Gram-Positive Bacteria.

    PubMed

    Biswas, Bipul; Rogers, Kimberly; McLaughlin, Fredrick; Daniels, Dwayne; 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  μ L 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.

  10. Comparative in vitro activity of gemifloxacin against gram-positive and gram-negative clinical isolates in Argentina.

    PubMed

    Lopez, H; Stepanik, D; Vilches, V; Scarano, S; Sarachian, B; Mikaelian, G; Finlay, J; Sucari, A

    2001-08-01

    The in vitro activity of gemifloxacin against 1,000 clinical isolates of 147 Streptococcus pneumoniae (115, penicilin susceptible; 26, intermediate penicillin-resistant and 6, penicillin-resistant), 127 Hemophilus influenzae (109, beta lactamasa non-producer; 18, beta lactamase producers), 95 Streptococcus pyogenes (6, azytromycin-resistant), 84 Moraxella catarrhalis (79, beta lactamase producers), 110 Staphilococcus aureus (89, methicillin-susceptible; 21, methicilin-resistant), 98 Eenterococcus faecalis and 339 Enterobacteriacea, (recovered from patients with respiratory tract infection; skin and soft tissue infection and urinary tract infection), was compared with the activities of four fluorquinolones and five other antimicrobial agents. Of the quinolones tested, gemifloxacin was the most potent against Streptococcus pneumoniae, including penicillin intermediate and resistant strains. Mic(90) values obtained for gemifloxacin, ciprofloxacin, ofloxacin, levofloxacin and trvafloxacin were 0.03, 2, 2, 1 and 0.25 mg/L respectively. Gemifloxacin was 16 fold more potent than ciprofloxacin against methicillin-susceptible Staphylococcus aureus and 32 fold more potent than ciprofloxacin against Streptococcus pyogenes. When tested against Hemophilus influenzae, Moraxella catarrhalis and Enterobacteriaceae, all the quinolones showed similar activity. Our results demonstrate that gemifloxacin has similar activity than the other quinolones tested against Gram-negative organisms and is considerably more potent against Gram-positive organisms.

  11. 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.

  12. 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.

  13. Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria.

    PubMed

    Fischer, Carol L; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

    2012-03-01

    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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Positional effects of hydroxy groups on catalytic activity of proton-responsive half-sandwich Cp*Iridium(III) complexes

    DOE PAGES

    Suna, Yuki; Fujita, Etsuko; Ertem, Mehmed Z.; ...

    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

  20. Estimating the prevalence of active Helicobacter pylori infection in a rural community with global positioning system technology-assisted sampling.

    PubMed

    Melius, E J; Davis, S I; Redd, J T; Lewin, M; Herlihy, R; Henderson, A; Sobel, J; Gold, B; Cheek, J E

    2013-03-01

    We investigated a possible outbreak of H. pylori in a rural Northern Plains community. In a cross-sectional survey, we randomly sampled 244 households from a geocoded emergency medical system database. We used a complex survey design and global positioning system units to locate houses and randomly selected one eligible household member to administer a questionnaire and a 13C-urea breath test for active H. pylori infection (n = 166). In weighted analyses, active H. pylori infection was detected in 55·0% of the sample. Factors associated with infection on multivariate analysis included using a public drinking-water supply [odds ratio (OR) 12·2, 95% confidence interval (CI) 2·9-50·7] and current cigarette smoking (OR 4·1, 95% CI 1·7-9·6). People who lived in houses with more rooms, a possible indicator of decreased crowding in the home, were less likely to have active H. pylori infections (OR 0·7, 95% CI 0·5-0·9 for each additional room).

  1. 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

  2. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells.

    PubMed

    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

    2014-07-01

    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.

  3. 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.

  4. Highly active antiretroviral therapy is associated with decreased incidence of sexually transmitted diseases in a Taiwanese HIV-positive population.

    PubMed

    Cheng, Shu-Hsing; Yang, Chin-Hui; Hsueh, Yu-Mei

    2013-03-01

    There are reports of increased sexual risk behaviors in the HIV-positive population since the introduction of highly active antiretroviral therapy (HAART). Little is known about the effects of the case management (CM) program and HAART on sexually transmitted diseases (STDs) in Taiwan. HIV-positive subjects, who visited the outpatient clinics of Taoyuan General Hospital between 2007 and 2010, were enrolled. A total of 574 subjects and 14,462 person-months were reviewed. Incident STDs occurred in 104 (18.1%) subjects, and the incidence rate was 8.6 (95% confidence interval [CI], 7.1-10.5) per 100 person-years (PY). For men who have sex with men (MSM), heterosexual men and women, and injection drug users (IDU), 19.4 per 100 PY(95% CI, 15.7-24.0), 3.5 per 100 PY (95% CI, 1.4-7.3), and 1.1 per 100 PY (95% CI, 0.4-2.4) of STDs were noted, respectively; (MSM versus IDU and MSM versus heterosexual subjects, p<0.000001; heterosexual subjects versus IDU, p=0.061). Syphilis (59.6%) was the most common STD. Regular CM and no HAART (hazard ratio, 2.58; 95% CI, 1.14-5.84; p=0.02) was significantly associated with STDs in MSM. Though this retrospective study might underestimate the incidence of STDs and not draw the conclusion of causality, we concluded that the CM program and HAART are associated with lower acquisition of STDs in the Taiwanese HIV-positive population.

  5. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity.

    PubMed

    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.

  6. 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.

  7. Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats.

    PubMed

    Zhu, Yi; Wang, Youping; Wang, Donna H

    2005-10-01

    To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9+/-2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5+/-10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9+/-2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis.

  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.

  9. 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.

  10. Effect of active region position in Fabry-Perot single transverse mode broad-waveguide InGaAsP/InP lasers.

    PubMed

    Lysevych, M; Tan, H H; Karouta, F; Jagadish, C

    2014-04-07

    The dependence of laser performance on the active region position in broad-waveguide laser diodes is presented in this paper. Performance of structures with different position of active region is compared in simulation and actual devices. Lasers with active region displaced towards the p-cladding layer outperformed the lasers with active region undisplaced or displaced towards the n-cladding layer both in simulation and experimentally. Maximum output power increased by 25% for devices with active region displaced towards the p-cladding layer.

  11. 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.

  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. Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy.

    PubMed

    Bibi, Siham; Arslanhan, Melis Dilara; Langenfeld, Florent; Jeanningros, Sylvie; Cerny-Reiterer, Sabine; Hadzijusufovic, Emir; Tchertanov, Luba; Moriggl, Richard; Valent, Peter; Arock, Michel

    2014-03-01

    Chronic myeloid leukemia and systemic mastocytosis are myeloid neoplasms sharing a number of pathogenetic and clinical features. In both conditions, an aberrantly activated oncoprotein with tyrosine kinase activity, namely BCR-ABL1 in chronic myeloid leukemia, and mutant KIT, mostly KIT D816V, in systemic mastocytosis, is key to disease evolution. The appreciation of the role of such tyrosine kinases in these diseases has led to the development of improved therapies with tyrosine kinase-targeted inhibitors. However, most drugs, including new KIT D816V-blocking agents, have failed to achieve long-lasting remissions in advanced systemic mastocytosis, and there is a similar problem in chronic myeloid leukemia, where imatinib-resistant patients sometimes fail to achieve remission, even with second- or third-line BCR-ABL1 specific tyrosine kinase inhibitors. During disease progression, additional signaling pathways become activated in neoplastic cells, but most converge into major downstream networks. Among these, the AKT and STAT5 pathways appear most critical and may result in drug-resistant chronic myeloid leukemia and systemic mastocytosis. Inhibition of phosphorylation of these targets has proven their crucial role in disease-evolution in both malignancies. Together, these observations suggest that STAT5 and AKT are key drivers of oncogenesis in drug-resistant forms of the diseases, and that targeting STAT5 and AKT might be an interesting approach in these malignancies. The present article provides an overview of our current knowledge about the critical role of AKT and STAT5 in the pathophysiology of chronic myeloid leukemia and systemic mastocytosis and on their potential value as therapeutic targets in these neoplasms.

  14. Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy

    PubMed Central

    Bibi, Siham; Arslanhan, Melis Dilara; Langenfeld, Florent; Jeanningros, Sylvie; Cerny-Reiterer, Sabine; Hadzijusufovic, Emir; Tchertanov, Luba; Moriggl, Richard; Valent, Peter; Arock, Michel

    2014-01-01

    Chronic myeloid leukemia and systemic mastocytosis are myeloid neoplasms sharing a number of pathogenetic and clinical features. In both conditions, an aberrantly activated oncoprotein with tyrosine kinase activity, namely BCR-ABL1 in chronic myeloid leukemia, and mutant KIT, mostly KIT D816V, in systemic mastocytosis, is key to disease evolution. The appreciation of the role of such tyrosine kinases in these diseases has led to the development of improved therapies with tyrosine kinase-targeted inhibitors. However, most drugs, including new KIT D816V-blocking agents, have failed to achieve long-lasting remissions in advanced systemic mastocytosis, and there is a similar problem in chronic myeloid leukemia, where imatinib-resistant patients sometimes fail to achieve remission, even with second- or third-line BCR-ABL1 specific tyrosine kinase inhibitors. During disease progression, additional signaling pathways become activated in neoplastic cells, but most converge into major downstream networks. Among these, the AKT and STAT5 pathways appear most critical and may result in drug-resistant chronic myeloid leukemia and systemic mastocytosis. Inhibition of phosphorylation of these targets has proven their crucial role in disease-evolution in both malignancies. Together, these observations suggest that STAT5 and AKT are key drivers of oncogenesis in drug-resistant forms of the diseases, and that targeting STAT5 and AKT might be an interesting approach in these malignancies. The present article provides an overview of our current knowledge about the critical role of AKT and STAT5 in the pathophysiology of chronic myeloid leukemia and systemic mastocytosis and on their potential value as therapeutic targets in these neoplasms. PMID:24598853

  15. 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

    2015-04-09

    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.

  16. The co-operative action of hyaluronidase and urokinase on the isoproterenol-induced myocardial infarction in rats.

    PubMed

    Borrelli, F; Antonetti, F; Martelli, F; Caprino, L

    1986-04-15

    The effects of the intravenous administration of hyaluronidase (HY; 2,500 IU/kg) and urokinase (UK; 20,000 and 40,000 IU/kg), alone or in combination, on the isoproterenol (ISP) induced myocardial infarction (MI) in rats, were studied. The severity of infarction was determined by measuring the levels of serum enzymes (CPK, GOT, LDH) and by evaluating the extent of the injured areas and the incidence of mortality. Plasma thromboxane B2 (TXB2) levels were also determined. All the treatments reduced the infarction area and the enzyme levels (increased by ISP) to a varying degree. However, a definite potentiating activity was obtained when HY was combined with the highest dose of UK. This combination was also capable of reducing the mortality rate. Finally, both HY and UK or the combined preparation brought the plasma TXB2 levels back to normal. These findings suggest the possibility of complementary activities of HY and UK in the treatment of experimental MI.

  17. Activation of Notch1 promotes development of human CD8(+) single positive T cells in humanized mice.

    PubMed

    Haji, Yoichi; Suzuki, Makiko; Moriya, Kunihiko; So, Takanori; Hozumi, Katsuto; Mizuma, Masamichi; Unno, Michiaki; Ishii, Naoto

    2014-05-02

    Notch1 mutations are found in more than 50% of human T cell acute lymphoblastic leukemia (T-ALL) cells. However, the functions of Notch1 for human T cell development and leukemogenesis are not well understood. To examine the role of Notch1, human hematopoietic stem cells (HSCs), which had been transduced with a constitutively active form of Notch1 (ICN1), were transplanted into severely immunodeficient NOD/Shi-scid-IL2rγ(null) (NOG) mice. We found that the great majority of the ICN1-expressing hematopoietic cells in the bone marrow expressed surface markers for T cells, such as CD3, CD4, and CD8, and that this T cell development was independent of the thymus. Accordingly, phenotypically mature CD8(+) single positive (SP) T cells were observed in the spleen. Furthermore, T-ALL developed in one NOG recipient mouse out of 26 that had been secondary transferred with the T cells developed in the first NOG mice. These results indicate that Notch1 signaling in HSCs promotes CD8(+) SP T cell development, and that T cell leukemogenesis may require additional oncogenic factors other than Notch1 activation.

  18. 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.

  19. In vitro activity of Oritavancin against gram-positive pathogens isolated in Canadian hospital laboratories from 2011 to 2015.

    PubMed

    Karlowsky, James A; Walkty, Andrew J; Baxter, Melanie R; Arhin, Francis F; Moeck, Gregory; Adam, Heather J; Zhanel, George G

    2017-04-01

    Gram-positive bacterial pathogens isolated from patient specimens submitted to 15 Canadian hospital laboratories from 2011 to 2015 were tested in the coordinating laboratory for susceptibility to oritavancin and comparative antimicrobial agents using the Clinical and Laboratory Standards Institute M07-A10 (2015) broth microdilution method. Oritavancin's in vitro activity was equivalent to, or more potent than, vancomycin, daptomycin, linezolid, and tigecycline against methicillin-susceptible Staphylococcus aureus (n=2680; oritavancin MIC90, 0.12μg/mL; 99.9% oritavancin-susceptible), methicillin-resistant S. aureus (n=728; oritavancin MIC90, 0.12μg/mL; 99.7% oritavancin-susceptible), Streptococcus pyogenes (n=218; oritavancin MIC90, 0.25μg/mL; 100% oritavancin-susceptible), Streptococcus agalactiae (n=269; oritavancin MIC90, 0.12μg/mL; 100% oritavancin-susceptible), and vancomycin-susceptible Enterococcus faecalis (n=508; oritavancin MIC90, 0.06μg/mL; 100% oritavancin-susceptible). Oritavancin, dalbavancin, and telavancin demonstrated equivalent in vitro activities (MIC90, μg/mL) against 602 isolates of MSSA (0.06, 0.06, 0.06, respectively) and 144 isolates of MRSA (0.12, 0.06, 0.06, respectively) collected in 2015.

  20. 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

  1. 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.

  2. Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation.

    PubMed

    Van Roey, Kim; Davey, Norman E

    2015-12-01

    A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilita