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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Rafelski, Johann; Ericson, Torleif;
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ SpringerOpenarrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ SpringerOpenarrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    All set for college summer arts festival -- Choir in concert -- Open reading on Thursday -- Captain Cook film, lectures on Saturday -- New sawmill training program -- Salt Lake choir on Sunday -- Lunchtime theatre finale -- Man of la mancha starts -- Treat for gourmets -- New books here -- Revised gymnasium hours -- Fitness week April 17-22 -- New student council -- Art show extensive -- Beddows a winner -- Meet the artist - Jo Merrill https://viuspace.viu.ca/bitstream/handle/10613/636/MainlyMalApr10-78.pdf?sequence=3

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ VIUSpacearrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    VIUSpace
    2013
    Data sources: VIUSpace
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ VIUSpacearrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      VIUSpace
      2013
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Tian, Haozhan;

    Compact antenna has been widely used due to its advantage of compact size and low fabrication cost. With the development of communication, antennas with unique radiation features are required for different scenarios. For example, beam steering is desired for 5G; while endfire radiation is for vehicle-to-vehicle communications. These requirements bring new challenges to the design of the compact antenna. In order to realize the features, designers always have to compromise on size, robustness, or fabrication cost. To alleviate this problem, we propose a new design method that applies coupled modes into the compact antenna designs. In this dissertation, beam steering antenna, endfire antenna with vertical polarization, and circularly-polarized antenna are demonstrated respectively. All the proposed antennas remain compact, robust, and cost-efficient. In addition, the coupled-mode concept is further extended to design reflector array. The proposed retro-reflective grating array works for wide-band incoming wave with any polarization. Other possible applications of the proposed concept are also discussed.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Clark, Ashley;

    By studying the disproportionate catastrophic effects on Manila City and Makati City caused by flooding associated with Typhoon Ondoy (international name: Ketsana) in 2009 this thesis examines how resilient disaster recovery projects in Metro Manila support state myth-making activities pursued at various scales of governance to justify the expansion of territorial control. Political authorities in Metro Manila rely on resilience discourses to legitimize resilience interventions in the aftermath of a disaster, and these interventions are often to the detriment of those most socio-environmentally vulnerable. Drawing on the dual disaster framework and perspectives from urban political ecology, this thesis concentrates on the variegated power of global urban resilience discourses and how these, in turn, impact resilient disaster recovery projects on the ground in Metro Manila. While national government officials argue it is an obligation of the state to make the city resilient, specifically by improving and building vital infrastructure; disasters, such as typhoon flooding cannot be neatly contained within jurisdictional boundaries and tend to spill over into neighbouring regions where there are overlapping areas of authority and competing interests – as demonstrated in the cases of Manila and Makati. As such, this thesis proposes two new theoretical concepts – shadow(s) of resilience and risk redistribution - in order to provide a contextualized understanding of urban spaces prior to change and account for the complex ways in which the socio-spatial realities of urban residents are altered due to the overlapping of natural and human-made disasters. Ultimately, resilient disaster recovery projects in Metro Manila contribute to an unequal redistribution of risks and resiliencies along axes of class, obscuring the role of state actors in creating these divides.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ QSpacearrow_drop_down
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    QSpace
    Other ORP type
    License: CC BY
    Data sources: QSpace
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      QSpace
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Pooyak, Eli; Littlepoplar, Alphonse;

    2 p. transcript of an interview with Eli Pooyak conducted by Alphonse Littlepoplar on November 25, 1974. Tape number IH-80, transcript disc 19. NOTE: This tape contains Cree songs by Eli Pooyak. These songs have not been translated. To follow in this document is the biography of Eli Pooyak. Other no

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ oURspacearrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    oURspace
    Other ORP type . 1974
    Data sources: oURspace
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ oURspacearrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      oURspace
      Other ORP type . 1974
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    https://viurrspace.ca/bitstream/handle/10613/20908/Sep20-1889.pdf?sequence=2&isAllowed=y

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    VIUSpace
    1889
    Data sources: VIUSpace
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      VIUSpace
      1889
      Data sources: VIUSpace
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Rothenberg, Lawrence S.;

    There has been much theorizing about why individuals join interest groups. However, little has been done to test the resulting propositions because of the difficulties associated with empirically analyzing the joining decision. This deficiency is especially great when it comes to public or symbolic interest groups. In this analysis, choice-based probability methods are employed that permit the combination of data from the 1980 National Election Study with comparable information about Common Cause members and the estimation of models of the participation calculus. Besides demonstrating the applicability of the choice-based methodology, this analysis shows the primary importance of political interest and policy preferences for the membership choice. Citizens who are politically interested and have preferences that roughly match an organization's reputation find that associational membership has both greater benefits and lower costs for them than it does for others. An ability to pay is irrelevant, regardless of educational attainment and despite members' high incomes. Organizational leaders deliberately keep the costs of membership low relative to most citizens' ability to pay; this encourages potential contributors to join in order to learn about the organization.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Caltech Authorsarrow_drop_down
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Hassanali, M.; Stothard, P.; Knox, C.; Wishart, D.S.; +3 Authors

    DrugBank is a unique bioinformatics/cheminformatics resource that combines detailed drug (i.e. chemical) data with comprehensive drug target (i.e. protein) information. The database contains .4100 drug entries including .800 FDA approved small molecule and biotech drugs as well as .3200 experimental drugs. Additionally, .14 000 protein or drug target sequences are linked to these drug entries. Each DrugCard entry contains .80 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Many data fields are hyperlinked to other databases( KEGG,PubChem, ChEBI, PDB, Swiss-Prot and GenBank) and a variety of structure viewing applets. The database is fully searchable supporting extensive text, sequence, chemical structure and relational query searches. Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. DrugBank is available at http:// redpoll.pharmacy.ualberta.ca/drugbank/.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Education and Resear...arrow_drop_down
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    Authors: Aghanoori, MohamadReza;

    Background: There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes exhibiting diabetic sensorimotor polyneuropathy (DSPN). We hypothesized that loss of direct insulin or insulin-like growth factor 1 (IGF-1) signaling in diabetes drives depression of AMPK activity and mitochondrial function, both contributing to development of DSPN. Methods: Age-matched control Sprague-Dawley rats and streptozotocin (STZ)-induced type 1 diabetic rats with/without IGF-1 therapy or insulin implants were used for in vivo studies. For in vitro studies, adult DRG neurons derived from control or STZ-diabetic rats were cultured under defined conditions and treated with/without IGF-1 or insulin. Activators or inhibitors targeting components of the insulin/IGF-1 signaling pathways were used to unravel the mechanism of insulin/IGF-1 action in DRG neurons. Results: Insulin increased Akt phosphorylation and neurite outgrowth, and augmented mitochondrial function in DRG cultures derived from control or type 1 diabetic rats. In STZ-diabetic rats insulin implants reversed thermal sensitivity, increased dermal nerve density and restored the expression/activity of respiratory chain proteins in DRG. Decreased expression of mRNAs for IGF-1, AMPKα2 and ATP5a1 (subunit of ATPase) occurred in DRG of diabetic vs. control rats. IGF-1 up-regulated mRNA levels of these genes in cultured DRG neurons from control or diabetic rats. IGF-1 elevation of mitochondrial function, mtDNA and neurite outgrowth was suppressed by inhibition of AMPK (via siRNA). IGF-1 therapy in diabetic rats reversed thermal hypoalgesia, raised corneal nerve density and prevented tricarboxylic acid (TCA) pathway metabolite build-up in the sciatic nerve. Endogenous IGF-1 gene expression in neurons of the DRG was suppressed by hyperglycemia and rescued by treatment with IGF-1 or the aldose reductase inhibitor, sorbinil. Transcription factors NFAT1 and CEBP-β bound to the IGF-1 promoter in DRG tissue at higher levels in control vs diabetic rats. Inhibition of endogenous IGF-1 down-regulated Akt S473 phosphorylation and background neurite outgrowth in cultured DRG neurons. Conclusions: Insulin/IGF-1 therapy elevates mitochondrial function via AMPK to drive axonal repair in DSPN. Downregulation of endogenous IGF-1 in DRG neurons in diabetes may contribute to the pathogenesis of DSPN.

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    Authors: Chagarlamudi, Pakiraiah;
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Rafelski, Johann; Ericson, Torleif;
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    All set for college summer arts festival -- Choir in concert -- Open reading on Thursday -- Captain Cook film, lectures on Saturday -- New sawmill training program -- Salt Lake choir on Sunday -- Lunchtime theatre finale -- Man of la mancha starts -- Treat for gourmets -- New books here -- Revised gymnasium hours -- Fitness week April 17-22 -- New student council -- Art show extensive -- Beddows a winner -- Meet the artist - Jo Merrill https://viuspace.viu.ca/bitstream/handle/10613/636/MainlyMalApr10-78.pdf?sequence=3

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    VIUSpace
    2013
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      VIUSpace
      2013
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    Authors: Tian, Haozhan;

    Compact antenna has been widely used due to its advantage of compact size and low fabrication cost. With the development of communication, antennas with unique radiation features are required for different scenarios. For example, beam steering is desired for 5G; while endfire radiation is for vehicle-to-vehicle communications. These requirements bring new challenges to the design of the compact antenna. In order to realize the features, designers always have to compromise on size, robustness, or fabrication cost. To alleviate this problem, we propose a new design method that applies coupled modes into the compact antenna designs. In this dissertation, beam steering antenna, endfire antenna with vertical polarization, and circularly-polarized antenna are demonstrated respectively. All the proposed antennas remain compact, robust, and cost-efficient. In addition, the coupled-mode concept is further extended to design reflector array. The proposed retro-reflective grating array works for wide-band incoming wave with any polarization. Other possible applications of the proposed concept are also discussed.

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    Authors: Clark, Ashley;

    By studying the disproportionate catastrophic effects on Manila City and Makati City caused by flooding associated with Typhoon Ondoy (international name: Ketsana) in 2009 this thesis examines how resilient disaster recovery projects in Metro Manila support state myth-making activities pursued at various scales of governance to justify the expansion of territorial control. Political authorities in Metro Manila rely on resilience discourses to legitimize resilience interventions in the aftermath of a disaster, and these interventions are often to the detriment of those most socio-environmentally vulnerable. Drawing on the dual disaster framework and perspectives from urban political ecology, this thesis concentrates on the variegated power of global urban resilience discourses and how these, in turn, impact resilient disaster recovery projects on the ground in Metro Manila. While national government officials argue it is an obligation of the state to make the city resilient, specifically by improving and building vital infrastructure; disasters, such as typhoon flooding cannot be neatly contained within jurisdictional boundaries and tend to spill over into neighbouring regions where there are overlapping areas of authority and competing interests – as demonstrated in the cases of Manila and Makati. As such, this thesis proposes two new theoretical concepts – shadow(s) of resilience and risk redistribution - in order to provide a contextualized understanding of urban spaces prior to change and account for the complex ways in which the socio-spatial realities of urban residents are altered due to the overlapping of natural and human-made disasters. Ultimately, resilient disaster recovery projects in Metro Manila contribute to an unequal redistribution of risks and resiliencies along axes of class, obscuring the role of state actors in creating these divides.

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    Authors: Pooyak, Eli; Littlepoplar, Alphonse;

    2 p. transcript of an interview with Eli Pooyak conducted by Alphonse Littlepoplar on November 25, 1974. Tape number IH-80, transcript disc 19. NOTE: This tape contains Cree songs by Eli Pooyak. These songs have not been translated. To follow in this document is the biography of Eli Pooyak. Other no

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    oURspace
    Other ORP type . 1974
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    https://viurrspace.ca/bitstream/handle/10613/20908/Sep20-1889.pdf?sequence=2&isAllowed=y

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    VIUSpace
    1889
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      VIUSpace
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    Authors: Rothenberg, Lawrence S.;

    There has been much theorizing about why individuals join interest groups. However, little has been done to test the resulting propositions because of the difficulties associated with empirically analyzing the joining decision. This deficiency is especially great when it comes to public or symbolic interest groups. In this analysis, choice-based probability methods are employed that permit the combination of data from the 1980 National Election Study with comparable information about Common Cause members and the estimation of models of the participation calculus. Besides demonstrating the applicability of the choice-based methodology, this analysis shows the primary importance of political interest and policy preferences for the membership choice. Citizens who are politically interested and have preferences that roughly match an organization's reputation find that associational membership has both greater benefits and lower costs for them than it does for others. An ability to pay is irrelevant, regardless of educational attainment and despite members' high incomes. Organizational leaders deliberately keep the costs of membership low relative to most citizens' ability to pay; this encourages potential contributors to join in order to learn about the organization.

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    Authors: Hassanali, M.; Stothard, P.; Knox, C.; Wishart, D.S.; +3 Authors

    DrugBank is a unique bioinformatics/cheminformatics resource that combines detailed drug (i.e. chemical) data with comprehensive drug target (i.e. protein) information. The database contains .4100 drug entries including .800 FDA approved small molecule and biotech drugs as well as .3200 experimental drugs. Additionally, .14 000 protein or drug target sequences are linked to these drug entries. Each DrugCard entry contains .80 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Many data fields are hyperlinked to other databases( KEGG,PubChem, ChEBI, PDB, Swiss-Prot and GenBank) and a variety of structure viewing applets. The database is fully searchable supporting extensive text, sequence, chemical structure and relational query searches. Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. DrugBank is available at http:// redpoll.pharmacy.ualberta.ca/drugbank/.

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    Authors: Aghanoori, MohamadReza;

    Background: There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes exhibiting diabetic sensorimotor polyneuropathy (DSPN). We hypothesized that loss of direct insulin or insulin-like growth factor 1 (IGF-1) signaling in diabetes drives depression of AMPK activity and mitochondrial function, both contributing to development of DSPN. Methods: Age-matched control Sprague-Dawley rats and streptozotocin (STZ)-induced type 1 diabetic rats with/without IGF-1 therapy or insulin implants were used for in vivo studies. For in vitro studies, adult DRG neurons derived from control or STZ-diabetic rats were cultured under defined conditions and treated with/without IGF-1 or insulin. Activators or inhibitors targeting components of the insulin/IGF-1 signaling pathways were used to unravel the mechanism of insulin/IGF-1 action in DRG neurons. Results: Insulin increased Akt phosphorylation and neurite outgrowth, and augmented mitochondrial function in DRG cultures derived from control or type 1 diabetic rats. In STZ-diabetic rats insulin implants reversed thermal sensitivity, increased dermal nerve density and restored the expression/activity of respiratory chain proteins in DRG. Decreased expression of mRNAs for IGF-1, AMPKα2 and ATP5a1 (subunit of ATPase) occurred in DRG of diabetic vs. control rats. IGF-1 up-regulated mRNA levels of these genes in cultured DRG neurons from control or diabetic rats. IGF-1 elevation of mitochondrial function, mtDNA and neurite outgrowth was suppressed by inhibition of AMPK (via siRNA). IGF-1 therapy in diabetic rats reversed thermal hypoalgesia, raised corneal nerve density and prevented tricarboxylic acid (TCA) pathway metabolite build-up in the sciatic nerve. Endogenous IGF-1 gene expression in neurons of the DRG was suppressed by hyperglycemia and rescued by treatment with IGF-1 or the aldose reductase inhibitor, sorbinil. Transcription factors NFAT1 and CEBP-β bound to the IGF-1 promoter in DRG tissue at higher levels in control vs diabetic rats. Inhibition of endogenous IGF-1 down-regulated Akt S473 phosphorylation and background neurite outgrowth in cultured DRG neurons. Conclusions: Insulin/IGF-1 therapy elevates mitochondrial function via AMPK to drive axonal repair in DSPN. Downregulation of endogenous IGF-1 in DRG neurons in diabetes may contribute to the pathogenesis of DSPN.

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