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The future of EPAC-targeted therapies: agonism versus antagonismParnell, E., Palmer, Timothy M., Yarwood, S.J. January 2015 (has links)
Yes / Pharmaceutical manipulation of cAMP levels exerts beneficial effects through the regulation of the exchange protein activated by cAMP (EPAC) and protein kinase A (PKA) signalling routes. Recent attention has turned to the specific regulation of EPAC isoforms (EPAC1 and EPAC2) as a more targeted approach to cAMP-based therapies. For example, EPAC2-selective agonists could promote insulin secretion from pancreatic β cells, whereas EPAC1-selective agonists may be useful in the treatment of vascular inflammation. By contrast, EPAC1 and EPAC2 antagonists could both be useful in the treatment of heart failure. Here we discuss whether the best way forward is to design EPAC-selective agonists or antagonists and the current strategies being used to develop isoform-selective, small-molecule regulators of EPAC1 and EPAC2 activity.
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Mötesplatsens mening och mål : Kund- och marknadstänkande inom folkbibliotekets förvaltningCarlson, Daniel January 2021 (has links)
Problemformulering och syfte: Bibliotekets styrning präglas av spänningar mellan ett demokratiskt uppdrag och en ekonomisk förvaltning. Syftet med uppsatsen är att studera motsättningen av folkbibliotekets styrning utifrån denna ideologiska spänning. Metod och teori: Genom kritisk ideologianalys analyseras tre kommuners biblioteksförvaltning; Nacka, Botkyrka och Stockholm, för att därefter belysas utifrån Chantal Mouffes politiska agonism och Jürgen Habermas borgerliga offentlighet. Material och resultat: Genom studier av kommunernas biblioteksplaner samt dokument för bemötandepolicy framkom det att Nacka kommun främst betonade en ekonomisk förvaltning, medan Botkyrka kommun främst betonade det demokratiska uppdraget och Stockholms stad placerade sig mellan dessa ytterligheter. Kommunernas ideologiska profilering kan betraktas utifrån politisk agonism och borgerlig offentlighet. Slutsatser: Kommunernas ideologiska styrning av biblioteken skiljde sig åt i termer av demokratiskt ansvar, ekonomisk förvaltning samt användarinteraktionen. Samtliga kommuner upprätthåller den liberala konsensusmodellen i olika hög grad vilket sammanfaller med deras koppling till NPM. Fler studier behövs för att utröna kommunala styrdokuments inverkan på biblioteksverksamheten. / Purpose: Library management is influenced by the opposition between democratic values and economic efficency. The purpose of this paper is to examine how the public library is influenced ideologically by this rift. Methodology and theory: Three municipalities, Nacka, Botkyrka and Stockholm are analyzed through critical ideological analysis, and then compared to Chantal Mouffe’s political agonism and Jürgen Habermas bourgeois public sphere. Materials and findings: Through library plans and treatment policys the outcome is that Nacka prioritizes financial stability, Botkyrka democratic values and Stockholm is situated somwhere inbetween. The municipalities ideologies can also be illuminated by theories of political agonism and public sphere by their perception of the public conversation. Implications: The municipal library administrations were separated through their ideological understanding of democratic values, user treatment, and financial management. The municipalities maintained the liberal consensus model to varying degrees, which coincides with their connection to NPM. More research is however needed for understanding the local government and its impact on the public library.
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Le conflit dans la communauté pluraliste chez Chantal MouffeGagnon-Tessier, Louis-Charles January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.
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Blogging Eurovision: An Unconventional Online Space for Everyday Political TalkSanikidze, Kakhi January 2017 (has links)
The paper starts by providing the overview of the Eurovision Song Contest, its participant countries and the audience. The aim of the research is to find out how everyday political talk takes place on non-political platforms. For this study, a blog dedicated to the Eurovision Song Contest was chosen. The research is netnographic, and the conclusions are drawn based on content analysis (the comments left on the Eurovision news blog - Wiwibloggs.com) and interviews with the journalists of the blog. The paper approaches the blog as anon-institutionalized space, also known as “the third space.” It covers issues such as nation branding, communication in an anonymous setting and deliberative democracy. The paper further analyses different characteristics of the content shared on the blog and answers a question on whether such content is agonistic or antagonistic by nature.
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Interações e conflitos entre humanos e macacos-prego (Cebus apella) no Parque da Criança em Anápolis-GO / Interactions and conflicts between humans and Capuchin Monkeys (Cebus apella) in Children Park of Anápolis-GOMartins, Lilian Betania Rocha 16 June 2005 (has links)
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Previous issue date: 2005-06-16 / There has been an increase in the number of conflicts between Capuchin-monkeys
(Cebus apella) and humans in municipal parks. Diminishing these conflicts has been a
big challenge as it has to find permanent solutions that benefit both parts. In this study I
investigated how the interactions between humans and capuchins occur, what people
think about the presence of these animals and how they behave towards them. Ad
libitum observations were conducted and video tapes made of interactions in one park,
in the city of Anápolis, State of Goiás, Brazil. Behavioral data were collected using
one/zero sampling, and all occurrences technique. Personal impressions were obtained
trough interviews with park users. The results obtained were analyzed in search of the
unleashing agent of agonism, including details about the days of the week on which
these conflicts were more likely to occur, whether or not food items were involved,
where in the park these interactions occurred, which types of behaviors are more
frequent, how and who intervened in the encounters etc. I also attempted to delineated a
profile of the persons that frequented the park, considering their opinion about the
monkey attacks on people, how they perceive the threats by the monkeys and their
opinions about the existence of monkey free urban areas. Results show that the majority
of the interactions occurred during the weekends. The wooded area was the place where
they most frequently occurred and the conflicts occurred more likely in the playground
area. Food transportation appears to be an important factor in the occurrence of
conflicts, but simply toting bags did not lead to conflicts. During conflicts the monkeys
emitted more combinations of different aggressive behaviors than did humans, but on
the other hand humans produced a greater number of non-aggressive behaviors. There
were more aggressive encounters when only humans emitted aggressive behaviors. The
majority of visitors were regulars, had a secondary level education, had up to three
offspring and visited the park for ecological reasons (which included see the monkeys
and nature viewing). These people remained in the park from one to four hours at a time,
and reported spending more time in the playground and wooded areas. More than half of
the interviewed reported stopping to watch the monkeys and some reported speaking to
the monkeys, feeding and attempting to touch them. Few admitted having attempted to
hurt them, but more than half had already witnessed other people doing so. A few had
seen the monkeys attacking humans. Attacks on humans by monkeys were one of the
reasons most commonly cited for the monkey attacks; the second reason was the lack of
food. Most people said they like the monkeys and thought they should remain in the
park, where educational programs should be conducted. The conclusion drawn was that
the attacks on humans by the monkeys were elicited by humans behavior: by monkeys
misinterpretation of the action of humans as aggressive; by reacting to human
interference in their social interactions, by being attacked first by humans, as a form of
obtaining food or other survival issues. On the other hand there was a lack of knowledge
about these animals on behalf of the visitors. This problem could be eliminated through
environmental education programs. / Tem havido um grande número de ocorrências de conflitos envolvendo macacos-prego
(Cebus apella) e humanos nos parques municipais. Harmonizar esses conflitos tem sido
um grande desafio e encontrar soluções para os problemas gerados torna-se cada dia
mais urgente. O presente trabalho procurou investigar como se estabelecem essas
relações e o que as pessoas pensam a respeito da presença desses animais no parque e
sobre a forma como se comportam. Para tanto, foram realizadas observações ad libitum,
filmagens no Parque da Criança, em Anápolis, Goiás, Brasil. Foram realizadas
observações diretas das interações, utilizando-se o método zero e um, registro de todas
as ocorrências e durante as observações foram anotadas informações contextuais
consideradas importantes. Também foram realizadas entrevistas com os freqüentadores
do parque. Os resultados mostraram que ocorreram mais interações nos finais de
semana. A mata foi o local em que houveram mais registros de interações e nos
brinquedos ocorreram mais interações conflituosas. O transporte de alimentos é um
fator importante para a ocorrência de interações conflituosas, já o de sacolas e outros
objetos não favoreceu esse tipo de interação. Em interações conflituosas os macacos
emitem um maior número de combinações de comportamentos agressivos que os
humanos, por outro lado os humanos, emitiram maior número de combinações contendo
categorias não agressivas. Houve mais interações agressivas quando só humanos
emitiram comportamentos agressivos do que quando só macacos emitiram tais
comportamentos. A maioria dos entrevistados consistiu de visitantes assíduos do parque,
que cursaram na sua maioria até o ensino fundamental e possuíam até três filhos. Tais
visitantes iam ao parque por questões ecológicas, entre elas, ver os animais, macacos e
apreciar a natureza. Costumavam permanecer no parque entre uma e quatros horas.
Disseram permanecer mais tempo nos brinquedos e na mata. Mais da metade disse
apenas olhar e parar para olhar os macacos, alguns disseram falar com animais,
alimentá-los e tentar tocá-los ou tocá-los. Muitos poucos confessaram já terem agredidoos,
mas, mais da metade já viram humanos agredirem os macacos e poucos viram os
macacos atacarem os humanos. O ataque ou agressão dos humanos aos macacos foi o
motivo mais citado para as agressões sofridas, seguida da falta alimentos. A maioria
disse gostar dos animais, e considera que deveriam permanecer no parque e que deveria
haver programas de educação ambiental. Concluiu-se que os ataques dos macacos aos
humanos de forma geral foram eliciados por ação de humanos: seja porque os macacos
interpretavam as atitudes dos humanos como ameaças, por terem sido atacados primeiro
pelos humanos, por reagirem à interferência humana em suas interações sociais, e como
forma de obtenção de recursos alimentares, ou ainda, por questões ligadas à sua
sobrevivência. Por outro lado, faltou aos humanos conhecimento adequado sobre esses
animais, sua importância e de como e quando interagir com eles, o que poderia ser
erradicado com a implantação de um programa de educação ambiental.
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The Other Side of the Medal : A Case Study of Right-Wing Populist Party Identity in German Newspaper DiscourseLehfeldt, Fabia Federica January 2018 (has links)
Nowadays, liberal democratic societies comprise the breeding ground for thriving right-wing populist parties. They share the “fundamental core of ethno-nationalist xenophobia, (…) and anti-political establishment populism” (Rydgren, 2004 p.475). Coeval research has acknowledged the threat that is entailed in the bespoken phenomenon; yet, its account is incomplete. This study follows Ernesto Laclau and Chantal Mouffe, in objecting to the individualist and rationalist tenets that inform previous research, to accentuate a neglected lens on the thrive of right-wing populism in Western liberal democracies. Their discourse theoretical frame was herein used as both theory and method, in a discourse analysis of the Alternative für Deutschland’s (AfD) identity in German online newspaper discourse. The empirical material comprised 97 articles from Germany’s most popular national daily newspapers, which reported on the AfD in parliament, an AfD demonstration in Berlin, and the AfD’s youth organisation’s congress throughout April, May and June 2018. Ultimately, the study arrived at the conclusion that the sampled newspaper discourse identified ‘us’, the ‘benevolent democrats’ via the exclusion, and rejection of ‘them’, the ‘wicked right-wing populists’. Since such relation was markedly antagonistic proper, newspaper discourse may be considered to have contributed to the recent thrive of right-wing populism in Germany.
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Characterisation of the α2A-adrenoceptor antagonism by mirtazapine and its modifying effects on receptor signalling / Kenneth KhozaKhoza, Kenneth January 2004 (has links)
Mirtazapine is an atypical antidepressant employed clinically for the treatment of major
depression. As a multipotent antagonist it acts at α2a-adrenergic receptors (α2a -ARs).
serotonin type-2A receptors (5-HT2a-Rs) and histamine type-I receptors (H1-Rs). Its actions
at the α2a-AR have been proposed to play a role in its putative earlier onset of action.
However, it is not known whether mirtazapine is a neutral antagonist or inverse agonist at α2a-
ARs. The current study aimed to determine the mode of α2a-AR antagonism by mirtazapine,
as well as to investigate in vitro the modulatory effects of mirtazapine pre-treatments on β-adrenergic
receptor (β-AR), muscarinic acetylcholine receptor (mAChR) and α2a-AR
functions.
Chinese hamster ovary (CHO-K1) cells expressing the porcine α2a-AR at high numbers (α2a-H),
a constitutively active mutant α2a-AR (α2a--CAM), or mock-transfected control cells (neo)
were radio-labelled with [3H]-adenine and concentration-effect curves of mirtazapine,
yohimbine, mianserin or idazoxan were constructed, measuring [3H]-cAMP accumulation. In
addition human neuroblastoma SH-SY5Y cells and CHO-K1 cells expressing the porcine α2a-
AR at low numbers (am-L) were used to investigate the effect of mirtazapine pre-treatments
on mAChRs and β-ARS or α2a-ARs respectively. After radio-labelling with myo-[2-3H]-inositol
or [2-%]-adenine, radio-label uptake was measured and receptor function was investigated
by constructing concentration-effect curves, measuring [3H]-IPx or [3H]-cAMP accumulation
respectively.
The results from the current study show that mirtazapine binds to the α2a-AR with an affinity
value in the lower micromolar range (K1≈ 0.32 µM; pK1 = 6.50 ± 0.07). Mirtazapine is not a
partial agonist at α2a-ARs as it does not affect [3H]-cAMP accumulation in α2a-H cells.
Preliminary results suggest that mirtazapine displays partial inverse agonism in α2a-CAM
cells, while mianserin displays neutral antagonism. Mirtazapine pre-treatment in SH-SY5Y
cells does not alter muscarinic receptor function (different from fluoxetine and imipramine),
but reduces I-isoproterenol-induced increase in [3H]-cAMP accumulation in SH-SY5Y cells
(typically associated with chronic antidepressant activity). Although inconclusive, the data
also suggests that mirtazapine may reduce α2a-AR function. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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Le conflit dans la communauté pluraliste chez Chantal MouffeGagnon-Tessier, Louis-Charles January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal
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Den europeiska offentliga sfären : En kritisk litteraturstudieWeissenbilder, Marcus, Müntzing, Fredrik January 2014 (has links)
Den offentliga sfären är ett begrepp som genom historien har definierats på en rad olika sätt. Detta har medfört att litteraturen om den europeiska offentliga sfären (EPS) har antagit en rad olika utgångspunkter. Vilket tidigare studier visar på finns det inom litteraturen på detta område ett antal brister i så väl operationaliseringar som konceptualiseringar. Denna kandidatexamen syftar till att, genom en litteraturstudie, utforska dessa olika konceptualiseringar kring EPS och även till att utreda huruvida forskningsfältet har förbättrats inom de olika områdena. Vårat resultat visar på att många metodologiska och konceptuella problem återstår inom forskningen om EPS och även att det finns en generell avsaknad av diskussion och kritik mot forskningens egna tillvägagångssätt. Vi vill också hävda att det Habermasiska perspektivet, och även forskning med fokus på massmedia och ett empiriskt perspektiv, är allt för dominerande. / The public sphere is a term which historically has been defined in various ways. This has caused the literature on the European public sphere (EPS) to take on many different viewpoints. As shown by previous studies, the literature on this subject has several flaws as well in its operationalization’s as in its conceptualization’s. This bachelor’s thesis sets out to, through a literature review, explore the different conceptualizations of the EPS as well as review whether the field of research has improved in the various areas. Our findings conclude that many methodological and conceptual issues remain in EPS research and there also seems to be a general lack of discussion and critique against the research’s own approaches. We would also argue that the Habermasian perspective, as well as research with a focus on mass media and an empirical perspective, is too dominant.
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Characterisation of the α2A-adrenoceptor antagonism by mirtazapine and its modifying effects on receptor signalling / Kenneth KhozaKhoza, Kenneth January 2004 (has links)
Mirtazapine is an atypical antidepressant employed clinically for the treatment of major
depression. As a multipotent antagonist it acts at α2a-adrenergic receptors (α2a -ARs).
serotonin type-2A receptors (5-HT2a-Rs) and histamine type-I receptors (H1-Rs). Its actions
at the α2a-AR have been proposed to play a role in its putative earlier onset of action.
However, it is not known whether mirtazapine is a neutral antagonist or inverse agonist at α2a-
ARs. The current study aimed to determine the mode of α2a-AR antagonism by mirtazapine,
as well as to investigate in vitro the modulatory effects of mirtazapine pre-treatments on β-adrenergic
receptor (β-AR), muscarinic acetylcholine receptor (mAChR) and α2a-AR
functions.
Chinese hamster ovary (CHO-K1) cells expressing the porcine α2a-AR at high numbers (α2a-H),
a constitutively active mutant α2a-AR (α2a--CAM), or mock-transfected control cells (neo)
were radio-labelled with [3H]-adenine and concentration-effect curves of mirtazapine,
yohimbine, mianserin or idazoxan were constructed, measuring [3H]-cAMP accumulation. In
addition human neuroblastoma SH-SY5Y cells and CHO-K1 cells expressing the porcine α2a-
AR at low numbers (am-L) were used to investigate the effect of mirtazapine pre-treatments
on mAChRs and β-ARS or α2a-ARs respectively. After radio-labelling with myo-[2-3H]-inositol
or [2-%]-adenine, radio-label uptake was measured and receptor function was investigated
by constructing concentration-effect curves, measuring [3H]-IPx or [3H]-cAMP accumulation
respectively.
The results from the current study show that mirtazapine binds to the α2a-AR with an affinity
value in the lower micromolar range (K1≈ 0.32 µM; pK1 = 6.50 ± 0.07). Mirtazapine is not a
partial agonist at α2a-ARs as it does not affect [3H]-cAMP accumulation in α2a-H cells.
Preliminary results suggest that mirtazapine displays partial inverse agonism in α2a-CAM
cells, while mianserin displays neutral antagonism. Mirtazapine pre-treatment in SH-SY5Y
cells does not alter muscarinic receptor function (different from fluoxetine and imipramine),
but reduces I-isoproterenol-induced increase in [3H]-cAMP accumulation in SH-SY5Y cells
(typically associated with chronic antidepressant activity). Although inconclusive, the data
also suggests that mirtazapine may reduce α2a-AR function. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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