263 research outputs found
Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons
No full textUnderstanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse in cocaine addiction often occurs following exposure to environmental stimuli previously associated with drug taking. The metabotropic glutamate receptor, mGluR5, is potentially important in this respect; it plays a central role in several forms of striatal synaptic plasticity proposed to underpin associative learning and memory processes that enable drug-paired stimuli to acquire incentive motivational properties and trigger relapse. Using cell type-specific RNA interference, we have generated a novel mouse line with a selective knock-down of mGluR5 in dopamine D1 receptor-expressing neurons. Although mutant mice self-administer cocaine, we show that reinstatement of cocaine-seeking induced by a cocaine-paired stimulus is impaired. By examining different aspects of associative learning in the mutant mice, we identify deficits in specific incentive learning processes that enable a reward-paired stimulus to directly reinforce behavior and to become attractive, thus eliciting approach toward it. Our findings show that glutamate signaling through mGluR5 located on dopamine D1 receptor-expressing neurons is necessary for incentive learning processes that contribute to cue-induced reinstatement of cocaine-seeking and which may underpin relapse in drug addiction.Original Publication:Martin Novak, Briac Halbout, Eoin C O'Connor, Jan Rodriguez Parkitna, Tian Su, Minqiang Chai, Hans S Crombag, Ainhoa Bilbao, Rainer Spanagel, David N Stephens, Gunther Schutz and David Engblom, Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons, 2010, JOURNAL OF NEUROSCIENCE, (30), 36, 11973-11982.http://dx.doi.org/10.1523/JNEUROSCI.2550-10.2010Copyright: Society for Neurosciencehttp://www.sfn.org
Confused about NMDA and Addiction? Targeted Knockouts Provide Answers and New Questions
No full textNMDA-dependent plasticity in VTA dopamine neurons has been hypothesized to be an important first step in the development of long-term changes in the brain reward circuitry that underlie addiction. Two papers from Zweifel et al. and Engblom et al. in this issue of Neuron raise new questions concerning the role of NMDA receptors within VTA dopamine neurons in mediating the behavioral effects of drugs of abuse
D5.1.1 Models of Real-time Applications on Service Oriented Infrastructures
No full textThe IRMOS project is developing tools and techniques for modelling, simulating, analysing, and planning real-time applications on service oriented infrastructures. These tools and techniques support the processes involved in designing, developing, deploying and executing applications where guaranteed QoS is needed. The report considers the value-chain for real-time applications hosted by third-party service providers. In the context of this value chain, we analyse who might benefit from the use of models, how and why these models might be used, and when during the application lifecycle modelling is most useful. Techniques are presented for building models of real-time applications including the use of stochastic process algebras, finite state automata, workflow models (e.g. BPEL, BPMN and YAWL) and specification languages (e.g. UML MARTE). The report discusses how these models need to be supported by estimation of application resource consumption, e.g. through benchmarking and fitting, and how mapping techniques allow models to be built for different actors in the value chain, e.g. for application providers and infrastructure providers. Tool support is also discussed e.g. PRISM for probabilistic model checking and Visual Service Composition Studio for service-oriented modelling. A detailed and specific real-time application scenario is included and modelled to allow the various techniques presented in this document to be demonstrated and quantitatively evaluated. The scenario also reveals the level of detail needed in order for meaningful modelling to be achieved in practice. The modelling scenario has been carefully engineered to be as representative as possible of the broad range of application characteristics encountered in the three reference IRMOS applications (film postproduction, eLearning, virtual and augmented reality). The modelling techniques discussed and then demonstrated in this report include identifying what resources are necessary to support an application, when those resources will be required during the application workflow, what performance is needed from them (i.e. QoS) and what will happen to the application if the required performance is not delivered. All of these are essential when developing and then agreeing service level agreements between the various entities in a service oriented infrastructure
The World´s Best Author is Not Female : An Analysis of Textbooks Regarding Female and Male Author Representation and Description in Textbooks for Swedish 2 in Upper Secondary School
No full textSyftet med denna studie är att undersöka vilket utrymme kvinnliga respektive manliga författare ges och hur de presenteras i läromedel i svenska 2 för gymnasiet. Inledningsvis presenteras vår teoretiska utgångspunkt som grundar sig i Yvonne Hirdmans genusteori och även centrala begrepp behandlas. Vi redogör för relevant tidigare svensk forskning gjord av Christoffer Dahl, Annica Danielsson och Caroline Graeske. Dessutom presenterar vi en australiensisk studie av Jackie F.K Lee och Peter Collins. Den tidigare forskningen sätts sedan i relation till vår studies resultat. Metoden vi använder för att uppnå studiens syfte är läromedelsanalys. Vi har dels använt oss av en kvantitativ innehållsanalys, dels en kvalitativ textanalys för att kunna besvara våra frågeställningar. För att strukturera vårt resultat har vi även använt oss tematisk analys för att kunna identifiera teman i materialet. Materialet som vi har använt är fyra läromedel anpassade efter Lgy 11 som behandlar kursen svenska 2 för gymnasiet. Resultatet från våra läromedelsanalyser visar att manliga författare dominerar i samtliga läromedel, men hur starkt de dominerar varierar mellan läromedlen och mellan avsnitten. Resultatet visar även att det finns en skillnad mellan hur kvinnliga och manliga författare presenteras och beskrivs i läromedlen. Dessutom visar resultatet att det finns skillnader i beskrivningarna av författarna i de olika läromedlen. I diskussionen lyfter vi de delar av resultatet från den tidigare forskningen som även går att se i vår studies resultat. Likväl diskuterar vi de delar av resultatet som skiljer sig från den tidigare forskningen. Vi diskuterar även att det har skett en förbättring gällande jämställdheten mellan kvinnliga och manliga författare i de läromedel som vi har granskat jämfört med den tidigare forskningen. Slutligen lyfter vi problematiken kring ansvaret att granska läromedel och vikten av att det genomförs.
Neural Mechanisms of Inflammation-Induced Fever
No full textFever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E-2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E-2 synthesis in these cells. The evidence for a role for other signaling routes for fever, such as signaling via circumventricular organs and peripheral nerves, as well as transfer into the brain of peripherally synthesized prostaglandin E-2 are yet far from conclusive. We also review the efferent limb of the pyrogenic pathways. We conclude that it is well established that prostaglandin E-2 binding in the preoptic hypothalamus produces fever by disinhibition of presympathetic neurons in the brain stem, but there is yet little understanding of the mechanisms by which factors such as nutritional status and ambient temperature shape the response to the peripheral immune challenge.Funding Agencies|Swedish Medical Research Council [07879, 20725]; European Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland</p
Revisiting metropolitan house price-income relationships
No full textFor helpful comments, we thank the editor Jeff Zabel and two anonymous reviewers, as well as Christian Hilber, Simon Lapointe and Oskari Vähämaa, and participants at the International AREUEA conference in Amsterdam, ARES conference in San Diego, ERSA conference in Cork, ERES conference in Delft, Annual Meeting of the Finnish Economic Association, and research seminar at the University of Cambridge. We also thank Andrew VanValin for preparing the maps. This work was supported by the Strategic Research Council at the Academy of Finland (first author; decision numbers 352450 and 352451) and the West-Finland Housing Association of Public Utility.Peer reviewe
Acoustic Analogy for Oscillations Induced by Supersonic Flow over a Forward-Facing Nose Cavity
No full textDet utdömda ledarskapet : En studie av laissez faire-ledarskapets påverkan på stressorerna krav, kontroll och stöd
No full textStudien syftar till att utöka förståelsen för hur laissez faire-ledarskapsstilen och de egenskaper som inkluderas i den upplevs påverka stressorerna krav, kontroll och stöd. Data har insamlats genom tolv semistrukturerade intervjuer. Resultatet påvisar att laissez faire-ledaregenskaperna kan innebära såväl för- som nackdelar för underställda i deras arbete. Två framträdande faktorer som påverkar effekterna har identifierats - dels mängden erfarenhet hos de underställda, dels frågan huruvida ledarens uppvisande av laissez faire-egenskaperna är ett strategiskt val eller beror på passivitet. Studien indikerar att laissez faire- ledarskap kan ge positiva effekter för de underställda, framför allt när det används som ett strategiskt val och när de underställda har lång erfarenhe
An evaluation of micropolar continuum theory in biomechanics
No full textTypescript (photocopy).The use of numerical analysis studies in biomechanics research continues to motivate the pursuit of improved models for biological materials. Micropolar continuum theory has been suggested by some to provide more complete descriptions of blood flow and bone behavior. Micropolar theory is an extension of classical continuum theory that introduces independent particle rotations and allows couple stresses. Solutions to relevant modeling problems of current interest are compared for micropolar and classical theory. For blood flowing through a stenosis, micropolar theory yields substantially higher wall shear stresses and slightly more flow recirculation. The extent of deviation from classical theory depends largely upon the choice of boundary conditions for the new independent particle rotation introduced by micropolar theory. In the case of bone behavior, micropolar theory yields significantly different stress fields in the compact bone tissue surrounding the screw hole of a fracture fixation plate. Micropolar solutions reveal higher stress concentrations and markedly increased distortion energy densities. The significant differences between micropolar and classical solutions for the practical modeling problems studied in this work suggest that further experimental and theoretical analyses aimed at better defining micropolar models for blood and bone are warranted
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