In this dissertation I introduce a simple experimental approach for studying afferent pain fibre physiology. I developed an en bloc dural-skull preparation that pairs electrophysiological stimulations, pharmacological manipulations, and the UV photolysis of caged compounds in and around selectively identified individual C-fibre nociceptors with microfluorometric imaging of Ca2+ responses. This allows the observation of physiological functioning in individual nociceptive fibre free nerve endings. I show high-resolution functional imaging of single action potential-evoked fluorescent transients, as well as sub- and supra-threshold calcium signaling events within individual nociceptive fibre terminations. Utilizing the dural-skull preparation I was able to identify a peripheral mechanism of action in the terminals of CGRP nociceptive fibres for an effective migraine therapeutic, the selective 5-HT1 receptor agonist, sumatriptan. I found sumatriptan to cause an approximately 40% reduction in the amplitude of action potential-evoked Ca2+ transients in the peripheral terminals of CGRP nociceptive fibres that was mediated selectively through the inhibition of N-type Ca2+ channels. Observations from this study support a peripheral site of action for sumatriptan in inhibiting the activity of dural pain fibres and adds to our understanding of the mechanisms that underlie the clinical effectiveness of 5-HT1 receptor agonists such as sumatriptan. While μ-opioid receptor agonists remain the most powerful analgesics for the treatment of severe pain, their mechanism of action in peripheral primary afferent pain fibres remain to be established. Further exploiting the dural-skull preparation I found activation of μ-opioid receptors in individual CGRP terminals had a dual modulatory effect; inhibition of N-type Ca2+ channel signaling and a frequency dependent, BKCa channel-mediated, suppression of action potential firing. These results establish possible anti-nociceptive mechanisms of μ-opioid receptor activation in the peripheral terminals of CGRP nociceptive fibres and identify new pathways to target for peripherally mediated analgesia. The development and subsequent testing of the dural-skull preparation in this dissertation displays its utility and opens up a new window for studying nociceptive fibre physiology and pathophysiology.

Flutter is one of the most important phenomena in which aerodynamic surfaces become unstable in certain flight conditions. Since the 1930&amp / #8217 / s many studies were conducted in the areas of flutter prediction in design stage, research of design methods for flutter prevention, derivation and confirmation of flutter flight envelopes via tests, and in similar subjects for aircraft wings. With the use of controllers in 1960&amp / #8217 / s, studies on the active flutter suppression began. First the classical controllers were used. Then, with the improvement of the controller synthesis methods, optimal controllers and later robust controllers started to be used. However, there are not many studies in the literature about fully movable control surfaces, commonly referred to as fins. Fins are used as missile control surfaces, and they can also be used as a horizontal stabilizer or as a canard in aircraft. In the scope of this thesis, controllers satisfying the performance and flutter suppression requirements of a fin are synthesized and compared. For this purpose, H2, Hinf, and mu controllers are used. A new flutter suppression method is proposed and used. In order to assess the performance of this method, results obtained are compared with the results of another flutter suppression method given in the literature. or the purpose of implementation of the controllers developed, aeroelastic model equations are derived by using the typical section wing model with thin airfoil assumption. The controller synthesis method is tested for aeroelastic models that are veloped for various flow regimes / namely, steady incompressible subsonic, unsteady incompressible subsonic, nsteady compressible subsonic, and unsteady compressible supersonic.

Denna uppsats är en studie av tre noveller skrivna av författare i den modernistiska grupp från Shanghai som brukar kallas nysensualisterna. Studien tar fasta på de olika sätt som författarna använder sig av blick och seende för att i de analyserade texterna uttrycka maktförhållanden, upphetsning och frustrationer i samband med den dramatiska materiella och intellektuella samhällsomvandling som 1920- och 1930-talets Shanghaibor ställdes inför och som bland annat kraftigt påverkade relationerna mellan män och kvinnor. I novellerna skildras hur de manliga huvudpersonerna – oavsett om de utsätts för andras blickar eller själva försöker sig på att använda blicken som ett maktinstrument – drivs till randen av ett sammanbrott på grund av den outhärdliga spänning som krocken mellan det nya och det gamla samhällets krav och förväntningar innebär. Blicken och seendet blir här ett tveeggat svärd som, när det används, tycks slå lika hårt mot den som svingar det som mot hans offer.

The sixteenth century was a time in which knowledge about the world grew exponentially in both its material content and the enthusiasm with which works treating of it were received. One of the most popular, long-lived and influential books of the kind was Sebastian Munster's Cosmographia, printed from 1544 to 1628, in 35 editions and five languages. The Cosmographia attempted nothing less than a geography of the whole known world, an encyclopaedia of its contents and a history of all its peoples. Based upon a close reading of the Latin 1550 edition of the Cosmographia. and supported by Munster's correspondence and other primary texts, this study examines several aspects of Munster's great work. A biographical chapter describes his Hebrew scholarship, the ethos of his humanist community and their influence upon his cosmography. The genre of cosmography, its ancient origins and development, are traced in the following chapter, as too are the alternative formulations favoured by his contemporaries. An account of the means by which Munster assembled the information for his book is next constructed, attending especially to his own empirical surveys and his creation of a learned network of those willing to do likewise. This chapter also surveys the printing, editions and reception of the Cosmographia. The final two chapters examine the contents and values of the book. They describe the organisation of the material and Munster's treatment of geography, history, ethnography, zoology and of prodigies of nature. The understanding of the world which emerges is analysed, addressing tolerance, identity, the high esteem of learning, and the reconciliation of faith with a burgeoning science. Also examined is Munster's concept of providence, which admonished the reader with the lessons of the fallen civilisations described in his Cosmographia, designed as a book of the world, an ark for its knowledge, and a Wunderkammer for its glories.

Made available in DSpace on 2016-06-02T19:05:17Z (GMT). No. of bitstreams: 1 DissMML.pdf: 1887422 bytes, checksum: 213fe8c28a477776b42e8c6ef861a171 (MD5) Previous issue date: 2003-08-21 / This work describes the implementation of a support structure to 3D virtual networked games, based on the emergent standard multiuser MPEG-4 in a Gnutella hybrid peer-to-peer network. This solution minimizes the disadvantages of the existent hybrid solutions, that they are based on proxies, which have to be re-configured whenever a new application appears in the net. For that, the code that implements the Gnutella network it was modified from way to include a service of search of games and of active sessions. Two defined components and specified by the emergent standard MPEG-4 MU were implemented and integrated into the Gnutella network for games session control and updating of the scenes. When a node designated as controller leaves, another should assume in a fast and continuous way. Those, among other challenges in the implementation of multiuser games as peer-to-peer applications, they will be discussed in this work, together with the integration of the technologies Gnutella and MPEG-4 MU. The evaluation of this implementation allowed to conclude the some topics about the adaptation of those networks in the support to applications that demand continuous collaboration, as it is the case of a 3D game in that multiples participant constantly alter the scene and also the viability of implementing a session controller in one of the nodes of the network. / Este trabalho descreve a implementação de uma estrutura de suporte a jogos virtuais 3D em rede, baseada no padrão emergente MPEG-4 multiusuário em uma rede Gnutella peer-to-peer híbrida. Esta solução minimiza as desvantagens das soluções híbridas existentes, que são baseadas em proxies, as quais têm que ser re-configuradas sempre que uma nova aplicação surge na rede. Para isso, o código que implementa a rede Gnutella foi modificado de modo a incluir um serviço de busca de jogos e de sessões ativas. Dois componentes definidos e especificados pelo padrão emergente MPEG-4 MU foram implementados e integrados à rede Gnutella para controle de sessão de jogos e atualização das cenas. Quando um nodo designado como controlador sai, outro deve assumir de forma rápida e contínua. Esses, entre outros desafios na implementação de jogos multiusuário como aplicações peer-to-peer, serão discutidos neste trabalho, juntamente com a integração das tecnologias Gnutella e MPEG-4 MU. A avaliação desta implementação nos permitiu chegar a algumas conclusões sobre a adequação dessas redes no suporte a aplicações que exigem colaboração contínua, como é o caso de um jogo 3D em que múltiplos participantes alteram a cena constantemente e também a viabilidade de se implementar um controlador de sessão em um dos nodos da rede.

<div> <p>Historically, natural products from plants, fungi, bacteria and animals have played an important role in the discovery of new drugs. In fact, it has been found that 34% of new FDA-approved drugs over the last 30 years were derived from natural products or their derivatives. Because of the chemical and structural diversity of natural products, they continue to be one of the best options for discovering novel compounds and scaffolds; this is especially true for compounds targeting the µ-, δ-, and κ- opioid receptors. However, traditional opioids such as morphine cause many therapeutically limiting side effects. Therefore, there have been immense efforts to develop opioids that avoid these side effects, with “signal-biased” compounds being an intense area of interest. The research presented here investigates of the biased mechanisms of compounds found in and derived from <i>Mitragyna speciosa</i>, also known as kratom, and <i>Picralima nitida</i>, also known as akuamma. Kratom and akuamma compounds are examined for their therapeutic potential in treating alcohol abuse and pain, respectively, two prevalent conditions with extreme societal and economic costs.</p> </div> <br>

Mu Columbae is a prototypical weak-wind O star for which we have obtained a high-resolution X-ray spectrum with the Chandra LETG/ACIS instrument and a low-resolution spectrum with Suzaku. This allows us, for the first time, to investigate the role of X-rays on the wind structure in a bona fide weak-wind system and to determine whether there actually is a massive hot wind. The X-ray emission measure indicates that the outflow is an order of magnitude greater than that derived from UV lines and is commensurate with the nominal wind-luminosity relationship for O stars. Therefore, the "weak-wind problem"--identified from cool wind UV/optical spectra--is largely resolved by accounting for the hot wind seen in X-rays. From X-ray line profiles, Doppler shifts, and relative strengths, we find that this weak-wind star is typical of other late O dwarfs. The X-ray spectra do not suggest a magnetically confined plasma-the spectrum is soft and lines are broadened; Suzaku spectra confirm the lack of emission above 2 keV. Nor do the relative line shifts and widths suggest any wind decoupling by ions. The He-like triplets indicate that the bulk of the X-ray emission is formed rather close to the star, within five stellar radii. Our results challenge the idea that some OB stars are "weak-wind" stars that deviate from the standard wind-luminosity relationship. The wind is not weak, but it is hot and its bulk is only detectable in X-rays.

No description available.

Undersökningens syfte är att göra en queeranalys av gestaltningen av temat familj i ett urval av nutida, svenska bilderböcker för barn. Undersökningens frågeställningar lyder: Vilken förståelse av begreppet familj kan en queerläsning ge utifrån antagandet att bilderböckernas respektive karaktärer tillsammans utgör var sin familj och vilka kriterier kan lägga grunden till alternativa definitioner av begreppet familj? De tre litterära verk som undersöks är Sune börjar skolan av Sören Olsson och Anders Jacobsson (Rabén &amp; Sjögren, 1997), När Findus var liten och försvann av Sven Nordqvist (Opal, 2001) samt Mamma Mu städar av Jujja och Tomas Wieslander med illustrationer av Sven Nordqvist (Natur och Kultur, 1997). Undersökningens frågeställningar besvaras med att alla tre litterära verk har potential att läsas queert. Undersökningen resulterar i ett antal kriterier som kontrasteras mot en traditionell definition av familj formulerat av Nationalencyklopedin, det vill säga kriterierna kan tillsammans utgöra en alternativ definition av begreppet familj.  Uppsatsen avslutas med en diskussion om bilderboken i samhället, nyttan av att läsa queert samt uppslag för framtida forskning.

在臨床上，許多疾病或藥物的使用會讓病患產生癢覺，而癢覺症狀的產生讓病患的日常生活品質下降，令人苦惱不已。因此，研究能夠抑制癢覺症狀的新藥物，是目前迫切需要的。臨床的研究發現，脊髓腔內注射類鴉片mu受體致效劑同時產生止痛與引發癢覺的功能。動物實驗也證明中樞給予類鴉片mu受體致效劑能引發搔癢的行為反應，而類鴉片kappa受體致效劑則可以降低類鴉片mu受體致效劑所引發的搔癢反應而不會干擾其止痛效果。本研究的目的，在於檢視類鴉片mu和kappa受體對於大白鼠的痛覺與癢覺的調控能力。藉由建立bombesin引發搔癢反應的動物行為模式，用以檢測實驗性藥物其抑制癢覺反應的功效，來比較類鴉片kappa受體致效劑、類鴉片mu受體拮抗劑以及組織胺受體拮抗劑對於bombesin所引發之搔癢反應的抑制效果。此外，並測試各類藥物在其引發癢覺或抑制癢覺時是否改變痛覺閾閥。最後，再透過側腦室給予類鴉片kappa受體拮抗劑來確認中樞神經系統裡類鴉片kappa受體在抗搔癢行為上的角色。研究結果得知兩項主要結論：（一）大白鼠的中樞類鴉片mu受體雖能抑制痛覺，但對於癢覺的傳遞或引發搔癢反應的功能有限。（二）不同類型的類鴉片kappa受體致效劑在無法抑制痛覺的低劑量範圍裡，都有抑制搔癢反應的效果。而且拮抗劑的使用，確認了中樞類鴉片kappa受體在抑制癢覺功能上的角色。相對於類鴉片mu受體拮抗劑及組織胺受體拮抗劑兩者都無法減緩bombesin所引發的搔癢反應，類鴉片kappa受體致效劑具有抑制不同根源的癢覺症狀的廣泛性。這些動物研究的發現有待進一步的臨床研究來確認類鴉片kappa受體致效劑作為新一代止癢藥物的潛在療效。 / Itch/pruritus is a symptom derived from several diseases or drug use that afflicts a large population of humans. It is important to study and develop novel drugs as antipruritics. Clinical studies have shown that intrathecal administration of mu opioid receptor agonists simultaneously produces analgesia and itch. Animal studies have also shown that centrally administered mu opioids can elicit itch/scratching responses and that kappa opioid receptor agonists can attenuate intrathecal morphine-induced scratching without interfering with antinociception. The aim of this study was to investigate the roles of mu and kappa opioid receptors in modulating pain and itch sensation in rats. Experiments were conducted to establish bombesin-induced scratching as an itch model to evaluate the antiscratching effectiveness of various drugs. A thermal nociceptive assay was used to examine whether drugs eliciting or inhibiting scratching can change rat’s nociceptive threshold. In addition, antagonist experiments were conducted to verify the receptor mechanism underlying the antiscratching effects of kappa opioids. Findings from a series of experiments suggest that central mu opioid receptors in rats have limited functions in expressing scratching responses. More importantly, kappa opioid receptor agonists, but not an opioid receptor antagonist or a histamine receptor antagonist, can attenuate bombesin-induced scratching. The antiscratching effects of kappa opioids occur at low and non-antinociceptive doses and such effects can be reversed by a kappa opioid receptor antagonist. These findings warrant additional clinical studies to document effectiveness of kappa opioid receptor agonists as antipruritics in a broader context.