There are currently many opioid agonists available for clinical use as analgesics. However, many of these opioid agonists have notorious side effects including respiratory depression and may lead to addiction and dependence. Problems associated with these opioid agonists are determined to come from their interactions with the mu-opioid receptor. Opioid antagonists, such as naltrexone, have shown to aid in the treatment of opioid addiction. Although naltrexone has high affinity to the mu-opioid receptor, it lacks selectivity. Novel selective mu-opioid receptor antagonists were designed based on the identification of important pharmacophore elements in several known mu-opioid receptor agonists and antagonists. These compounds were synthesized and in vitro biological assays were conducted to determine their affinity to all three opioid receptors. Also, molecular modeling studines were conducted to help visualize the interactions between the mu-opioid receptor and these ligands. Finally, four lead compounds have been identified for further optimization.

Thesis advisor: Alexa H. Veemena / Across species, the juvenile period is characterized by increased social interaction with peers and heightened novelty-seeking behavior, as compared to any other life stage. These behaviors are likely to be highly adaptive during this developmental phase. Still, an excessive novelty-seeking phenotype may predispose individuals to risk-taking and substance abuse, while too little social engagement and low novelty-seeking are characteristics of neuropsychiatry disorders such as autism. The over-arching aim of this dissertation research has been to elucidate the neural mechanisms underlying juvenile social novelty-seeking behavior. Central activation of oxytocin, vasopressin V1a, and µ-opioid receptors (OTR, V1aR, and MOR, respectively) have been implicated in the regulation of adult social behavior, but our understanding of the expression and function of OTR, V1aR, and MORs in the juvenile brain is incomplete. Therefore, in Studies 1 and 2, age differences in binding density of OTR, V1aR, and MOR throughout the rat brain were identified using receptor autoradiography. Next, in Study 3, I established the social novelty preference test, a new paradigm designed to assess the preference of juvenile rats to interact with either a novel or a familiar (cage mate) conspecific. Using this social novelty preference test, in Studies 3, 4, and 5, the functional involvement of OTR, V1aR, and MOR in the regulation of juvenile social novelty preference was characterized using both intracerebroventricular and local in-vivo pharmacological manipulations. The results of these experiments demonstrate that both OTR and MOR activation in the brain are involved in the regulation of juvenile social novelty preference, particularly acting within the nucleus accumbens. Finally, in Study 5, I investigated the impact of social isolation on juvenile social novelty preference. My findings show that social isolation potently reduces social novelty preference, which, in turn, can be restored by MOR activation in the nucleus accumbens. Taken together, this body of work significantly advances our understanding of the neural systems underlying juvenile social novelty preference, and suggests that both oxytocin and opioid systems in the brain may be potential clinical targets for restoring social novelty-seeking behavior in neurodevelopmental disorders, such as autism.

by Chan Wai-keung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves [116-121]). / Abstracts in English and Chinese. / CONTENTS / INTRODUCTION / Chapter CHAPTER 1. --- THE EARLY YEARS / Chapter CHAPTER 2. --- DISCURSION AND AMBIVALENCE: QIAN MU'S MIND ON CULTURE BEFORE1930 / Chapter CHAPTER 3. --- THE CULTURAL CONSERVATISM OF QIANMUFROM 1930 TO1949 / Chapter CHAPTER 4. --- THE CHOICE OF QIAN MU: AN INTERPRETATION / CONCLUSION / GLOSSARY / BIBLIOGRAPHY

No description available.

Syftet med studien är att undersöka hur några barn uppfattar och tolkar genus samt om och hur de i så fall identifierar sig med huvudrollsinnehavarna i Wieslanders bok Mamma Mu åker rutschkana. Dessutom är det av intresse att se om och på vilket sätt författaren till den valda boken skriver utifrån ett genusperspektiv. Boken i studien valdes subjektivt ut från en lista över de femtio mest utlånade barn- och ungdomsböcker på folkbiblioteken i Lunds kommun, 2010. Studien genomförs på en förskola i södra Sverige med tre flickor och tre pojkar i åldern fem år. Analysmetoden som används i studien är kvalitativ och bygger på en hermeneutisk analysmodell. Resultatet visar på att barnen såg Mamma Mu som en kvinna/flicka och Kråkan som en man/pojke samt att flickorna identifierar sig med Mamma Mu och pojkarna med Kråkan. Dessa identifieringar gör barnen utifrån kopplingen mellan deras kön och mellan deras personligheter. Dessutom kan vi se att text och bild påverkar barnen på olika sätt beroende på deras tidigare erfarenheter. Denna kunskap delar de med sig av till varandra vilket leder till att barnen får nya erfarenheter och en djupare förståelse av boken. Bokens författare antar främst barnens perspektiv när hon skriver vilket väl stämmer överens med genusperspektivet då det handlar om något större än enbart manligt och kvinnligt.

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Thesis (Ph. D.)--Hong Kong Baptist University, 2003. / Thesis submitted to the Dept. of Chinese Language and Literature. Includes bibliographical references (leaves 204-232).

Spectral efficiency is one of the most important measures of the performance of wireless communication systems owing to scarcity and cost of the radio spectrum. The increase in spectral efficiency provides higher data rates to the user, lower network cost to the operator, coverage extension and higher service reliability as well. Intercell interference due to frequency reuse is one of the key impairments in wireless systems. Multiple-input multiple-output (MIMO) technique has been developed to enhance the desired signal power (and hence mitigating the effects of intercell interference) and with employing simple linear signal processing technique, can strongly mitigate the interference resulting from co-channel users. This technique is mainly used to achieve spatial diversity for boosting the communication link reliability by combating fading, and providing spatial multiplexing to increase data rates without extra bandwidth by exploiting multipath. Distributed antenna system (DAS) has recently gained substantial interest due to its ability to reduce transmitted power thereby lowering the out-of-cell interference effects, maximise the coverage and improve the spectral efficiency. The combination of MIMO techniques with DAS, so-called distributed MIMO (D-MIMO) systems, is now being exploited and largely succeeded to fulfil the services of the fourth generation (4G) wireless systems. Very recently, one of crucial significance approach to reducing the radiated power and improving spectral efficiency to cope with fifth generation (5G) wireless systems is the use of large-scale MIMO (also referred to as massive MIMO) technology, which utilizes a large number of antennas, i.e., tens to hundreds, typically at the base station (BS) side. Presently, in the light of the rapid evolution of wireless systems into 5G, the integration of wireless power transfer (WPT) with newly wireless systems has seen a great deal of attention as a potential solution for powering energy-constrained wireless systems, especially with shortening communication links by emerging new technologies, e.g., D-MIMO and massive MIMO. This thesis is devoted to investigating and comparing the performance of three different MIMO systems. More specifically, the thesis focuses on analysing the spectral efficiency of a comprehensive model of self-powered MU-MIMO systems employing linear ZF technique at the BS for both perfect and imperfect channel state information (CSI) cases. The results demonstrate the impact of practical channel impairments, e.g., spatial correlation, shadowing and co-channel interference (CCI), and system parameters, e.g., the number of BS and user antennas, signal to noise ratio (SNR) and channel estimation error, on the spectral efficiency of the system. Besides, from a spectral efficiency perspective, a proposed model of a combination of MIMO and massive MIMO technologies with DAS in the presence of linear receivers at the processing unit (PU) is considered and compared to a centralised MIMO (CMIMO) system. The obtained results provide a wide range of insights into the effects of system parameters on the spectral efficiency and reveal that the proposed distributed MIMO system outperforms the C-MIMO system. In the context of wireless powered MIMO systems, this work investigates the performance of a power beacon (PB)-assisted wireless powered C-MIMO system, including one multi-antenna BS and a number of single-antenna users powered by randomly deployed PBs in the presence of ZF receiver at the BS. Also, two modes for radiation from the PBs are assumed and compared, one is the beamforming radiation mode (BRM), and the other is the isotropic radiation mode (IRM).

Made available in DSpace on 2016-08-29T15:37:10Z (GMT). No. of bitstreams: 1 tese_8353_Dissertação Julia 19_12.pdf: 3025929 bytes, checksum: dbee5dd0d2496a40249c81c0bb42ff2e (MD5) Previous issue date: 2014-12-04 / MOREAU, Julia Siqueira. Estruturae interação entre vegetação e ambiente de uma Floresta Ombrófila Densa das Terras Baixas, Espírito Santo. 2014. Dissertação (Mestrado em Ciências Florestais) Universidade Federaldo Espírito Santo, Jerônimo Monteiro, ES. Orientadora: Profª. Drª. Sustanis Horn Kunz. Coorientadores: Prof. Dr. Aderbal Gomesda Silvae Henrique MachadoDias O objetivo deste trabalho foi conhecer a estrutura e a composição de espécies da comunidade arbustiva-arbórea de um fragmento florestal de uma Floresta Ombrófila Densa das Terras Baixas, bem como verificar a interação da vegetação com as variáveis ambientais. Foram demarcadas 24 parcelas (20 x 20 m), totalizando 0,96 ha, onde foram medidos todos os indivíduos arbustivo-arbóreos com diâmetro a altura do peito &#8805; 2,5 cm. Além disso, foi calculada a porcentagem de abertura de dossel, por meio de fotografias hemisféricas, e realizada a caracterização química da camada superficial do solo (0 5 cm). Os dados foram correlacionados com a densidade absoluta de25 espécies que possuíam no mínimo 30 indivíduos (obtidas a partir da análise fitossociológica), por meio da Análise de Correspondência Canônica. Foram registrados 4.585 indivíduos e identificadas 379 espéciesdistribuídas em 195 gêneros e 66 famílias botânicas. A densidade foi de 4.604 ind./ha e a área basal foi 31,88 m²/ha. O índice de Shannon (H) encontrado para este estudo foi 5,41 e a equabilidade (J) foi 0,83, evidenciando a alta diversidade florística do fragmento e a sua semelhança com áreas bem preservadas da Mata Atlântica. A espécie de maior destaque em Valor de Importância (VI) foi Actinostemon klotzschii (Didr.) Pax, principalmente devido a densidade e frequência.Houve predominância de espécies secundárias tardias (51,9%) e de dispersão zoocórica (72,3%), evidenciando que o fragmento estudado está em bom estado de conservação. A partir da Análise de Correspondência Canônica foi possível comprovar que as variáveis fósforo, magnésio, matéria orgânica, nitrogênio, potássio e abertura de dosselexerceram influência sobre a distribuição das espécies deste fragmento (p<0,05), com destaque para a Xylopia frutescensAubl.que apresentou elevada correspondência com a porcentagem de abertura de dossel e para as espécies Actinostemon klotzschii(Didr.) Pax, Chrysophyllum lucentifoliumCronquist, Ecclinusa ramifloraMart.,Eugenia platyphyllaO.Berg e Rinorea bahiensis(Moric.) Kuntze que se desenvolveram em locais com menor necessidade de nutrientes. Com base no exposto, pode-se concluir que a vegetação possui alta riqueza de espéciese que as variáveis ambientais exercem influência sobre a distribuição das espécies deste fragmento indicando a possibilidade de implantação dessas espécies em locais com maior exposição a luminosidade e baixa fertilidade. Palavras-chave: Diversidade florística, Mata Atlântica, estrutura horizontal,variáveis ambientais.

L’utilisation des opioïdes est à l’origine de phénomènes de tolérance et d’hyperalgésie induite (HIO) aussi bien chez l’animal qu’en utilisation clinique. Ces phénomènes surviennent avec tous les opioïdes de manière dose-dépendante. Les mécanismes qui les sous-tendent sont complexes et imparfaitement connus. Le rémifentanil et le sufentanil sont les opioïdes les plus utilisés en France en anesthésie-réanimation. Leur utilisation s’accompagne d’une HIO qui majore la douleur postopératoire et peut être responsable de la persistance de la douleur à long terme. La perception des stimuli nociceptifs chez un patient sous anesthésie générale n’est pas aisée et repose encore sur des signes cliniques indirects d’activation du système sympathique. Ces signes peu sensibles et peu spécifiques conduisent à sous doser ou sur-doser les patients en opioïdes. Récemment, un nouvel outil de monitorage de la nociception est apparu, l’analgesia nociception index (ANI). L’ANI reflète le tonus parasympathique et de ce fait permettrait aux anesthésistes de mieux adapter le dosage des opioïdes. Dans cette thèse, nous avons d’abord évalué la sensibilité et la spécificité de l’ANI à détecter les stimuli nociceptifs, puis montré qu’elles étaient supérieures à celles des signes cliniques, et supérieures à d’autres indices de monitorage proposés. Ensuite nous avons validé la capacité de l’ANI à guider l’analgésie peropératoire du rémifentanil dans différentes situations.Sur le plan expérimental, nous avons exploré, après une exposition courte ou prolongée à différentes doses de rémifentanil et de sufentanil, les mécanismes associés à l’hyperalgésie thermique in vivo, chez la souris, et ex vivo, sur la voie des MAP kinases ERK1/2 et sur le trafic membranaire des récepteurs opioïdes de type µ (MOR) dans différentes cultures cellulaires. Chez la souris, nous avons mis en évidence une hyperalgésie précoce au saut sur plaque chaude, après exposition aux doses les plus élevées de rémifentanil, mais pas avec le sufentanil. De plus, nous n’avons pas observé d’HIO sur le léchage des pattes.Sur les cultures cellulaires, le rémifentanil comme le sufentanil activent la voie des MAPK ERK1/2 lors d’une exposition courte, avec apparition d’une désensibilisation lorsque l’exposition se prolonge. Le rémifentanil comme le sufentanil induisent une internalisation précoce et progressive des récepteurs MOR. / The use of opioids is associated with tolerance and induced hyperalgesia (OIH). Tolerance and OIH occur with all opioids and have been demonstrated both, in animals and in humans and are likely to be dose-dependent. The underlying mechanisms are complex and partially known. Remifentanil and sufentanil are the most used opioids in France in anesthesia and intensive care. Their use is associated with OIH that increases postoperative pain and may be responsible for persistent pain. In anesthetized patients, nociceptive stimuli are still detected according to clinical signs of sympathetic activation. These signs lack sensitivity and specificity and lead to underdosing or overdosing opioids. Recently, the analgesia nociception index (ANI), has been proposed as surrogate marker of nociception. The ANI reflects the parasympathetic tone and thus may allow anesthetists to better adapt the opioid dosage. In this thesis, we first evaluated the sensitivity and specificity of ANI to detect nociceptive stimuli, and showed that it better detects them than do clinical signs or than other currently available monitoring tools. Subsequently, we validated the ability of the ANI to adequately guide the intraoperative dosing of remifentanil in different clinical setting.After acute and sustained exposure to different doses of remifentanil and sufentanil we investigated, in vivo, the mechanisms associated with thermal hyperalgesia in mice, and ex vivo, the effect on the MAP kinase ERK1/2 pathway and the μ-type opioid receptor (MOR) membrane trafficking in human neuroblastoma and embryonic kidney cell cultures. In mice, high-dose remifentanil induced early hyperalgesia assessed by the jumping latency in a hot-plate test, but not the sufentanil. We did not observe OIH for the hind paw licking test. On cell cultures, after short exposure, both remifentanil and sufentanil produced activation of the MAP kinase ERK1/2 pathway, and rapid desensitization and internalization of the MOR.