Oocyte quality plays a critical role in establishment of pregnancies, embryo development, implantation and the health of offspring. The oocyte provides maternal factors necessary for the initial development of its embryo during the period of transcriptional silence. Despite the consistent increase in number of couples seeking assisted reproductive treatments, oocyte quality still remains as an obstacle in successful fertility treatments and the mechanisms governing the quality of oocyte are poorly understood. Among various factors that may potentially affect the quality of oocyte, the acquisition of oocyte developmental competence seems to mainly occur during the final stage of oocyte maturation. The correct temporal regulation of series of molecular events and the proper exchange of signals with surrounding follicular environment during this critical period will ensure the developmental competence of oocyte and its subsequent embryo. In order to identify molecular factors affecting oocyte quality, I have compared oocytes and cumulus cells of different qualities at a molecular level. I present in this thesis the pathways and molecules that may determine the developmental competence of oocyte as well as candidate molecular markers of oocyte and embryo quality. A cDNA microarray analysis was performed, comparing the transcriptomes of rhesus monkey MII oocytes of different qualities, high quality VVM oocytes and poor quality IVM oocytes. A small set of 59 Oocyte quality plays a critical role in establishment of pregnancies, embryo development, implantation and the health of offspring. The oocyte provides maternal factors necessary for the initial development of its embryo during the period of transcriptional silence. Despite the consistent increase in number of couples seeking assisted reproductive treatments, oocyte quality still remains as an obstacle in successful fertility treatments and the mechanisms governing the quality of oocyte are poorly understood. Among various factors that may potentially affect the quality of oocyte, the acquisition of oocyte developmental competence seems to mainly occur during the final stage of oocyte maturation. The correct temporal regulation of series of molecular events and the proper exchange of signals with surrounding follicular environment during this critical period will ensure the developmental competence of oocyte and its subsequent embryo. In order to identify molecular factors affecting oo was identified as differentially expressed between the two types of oocytes. These mRNAs are involved in steroid metabolism, cell-cell interactions, cellular homeostasis, cell adhesion, mRNA stability and translation. In addition, the overexpression of several imprinted genes in IVM oocytes were detected, indicating a possible loss of correct epigenetic programming during IVM. These results indicate that normal oocyte-somatic cell interactions may be disrupted during IVM and the interruptions of these interactions during the final phase of oocyte maturation may be the prime cause of reduced developmental competence of IVM oocytes. To elucidate oocyte quality factors linked to the cumulus cell phenotype, the transcriptomes of two types of rhesus monkey cumulus cells, IVM and VVM, were compared using a cDNA microarray analysis. In contrast to a relatively small difference between IVM and VVM oocytes, a large number of genes were differentially expressed between IVM and VVM rhesus cumulus cells. Moreover, a much larger number of differential mRNA expressions were observed comparing the transitions from pre-maturation cumulus cells to the IVM and VVM cumulus cells. The results from these array comparisons indicated that the cumulus cells may fail to achieve successfully normal gene regulation during IVM and thus make a remarkable amount of changes in gene expression to compensate for the loss. Numerous genes involved in lipid metabolism are incorrectly regulated during IVM, and the synthesis of sex hormones appears not suppressed during IVM. In addition, a panel of 24 cumulus cell markers of oocyte quality was identified. Genetic effects on oocyte quality were explored by comparing transcriptomes of oocytes obtained from two different inbred mouse strains, B6 and D2, and F1 hybrid. A clustering analysis and statistical tests showed that the transcriptome of F1 oocytes is more similar to the B6 transcriptome than to the D2 at both GV and MII stages. Also, comparison analyses of GV stage oocyte transcriptomes with MII oocyte transcriptomes from three different mouse strains indicated that the number of overdominance genes at the MII stage is bigger than the number of overdominance genes at the GV stage. In order to investigate how the genes gain the overdominance during the GV to MII transition, overdominance genes were categorized according to their mRNA expression patterns at GV and MII stages. The results showed that more than 80% of overdominance genes belong to one of the four major transition groups. The further evaluation of changes in array intensities from GV to MII stage transition revealed that F1 oocytes and inbred strain oocytes differentially regulate the mRNA abundance during oocyte maturation and that the differential regulation of mRNA abundance by the F1 genotype is responsible for the increase of the number of overdominance genes during maturation from GV stage to MII stage. A mRNA sequence analysis indicated that the gain of overdominant low in F1 mRNA expression pattern during maturation may be regulated by 3'UTR motif elements. The number of dominance genes also increase during GV to MII transition. At both GV and MII stages, there are more genes with B6 dominant mRNA expression pattern than those with D2 dominance pattern. Lipid metabolism, small molecule biochemistry and cell death are biofunctions overrepresented in both dominance and overdominance genes. In addition, `blebbing' was identified as a biofunction significantly downregulated in the F1 and B6 MII eggs, indicating that the cellular function may be involved in oocyte maturation. / Molecular Biology and Genetics / Accompanied by one .pdf file: YLEE_SupplementalTables.pdf

This dissertation examines monkey and ape iconography in Minoan art during the Aegean Bronze Age (ca. 3,000–1,100 B.C.). Although a broad range of animals exist for depiction, Minoan artists carefully selected each subject in order to fulfill specific roles. Monkeys and apes appear to function differently than the other creatures that are depicted in art. Rather than subscribing to the general roles played by other animals, these primates may be shown outdoors, behaving like wild animals, or in a ceremonial context, participating in a ritual. Monkeys also imitate human activities. The deviation of primates from the typical roles of other animals found in Minoan art invites a deeper investigation of the role and iconography of apes and monkeys. In this study, three types of media that bear depictions of primates are considered. These media include figurines, glyptic art, and wall paintings. First, a review of the stylistic features of Minoan art and the possibility for the use of pattern books is discussed. Next, monkey and ape iconography in Egyptian art is explored. A thorough review of the creatures’ iconography in Minoan art follows, which includes the identification of figures as either ape or monkey, as well as a detailed description and conclusions about each type of representation. A new possible reconstruction of the Saffron Gatherer fresco is also included. Finally, the possible origins of Minoan primate iconography are considered, as well as the possible implications of the creature’s history, development, and roles. With this information in mind, the Offering to the Seated Goddess scene is then examined. The possible reconstruction of a crocus ceremony is proposed and explained, and the Levantine parallels for the compositional arrangement of the scene are also addressed. These conclusions may directly inform greater themes in Minoan culture, such as religion and cult practices. / Art History

Denna kandidatuppsats undersöker de olika diskurser angående det övernaturliga som närvarar i Eden Robinsons roman Monkey Beach (2000) utifrån ett postkolonialt perspektiv. Det teoretiska ramverket består av Jo-Ann Episkenews indigenous storytelling, samt Michail Bachtins dialogicitetsbegrepp, där heteroglossi fungerar som utgångspunkt. Dessa har använts för att analysera hur Robinson använder sig av karaktärer för att gestalta olika epistemologier, och hur dessa relaterar till synen på det övernaturliga i romanen. Uppsatsens slutsats är att Monkey Beach är polyfon i sin gestaltning av de olika perspektiven på det övernaturliga; dessa perspektiv utgör olika diskurser, vilket gestaltas genom karaktärerna. Romanen utspelar sig inte i ett autonomt fiktivt universum; den fungerar som en motdiskurs till tidigare diskurser om urfolk i Kanada, vilket ger den både en avkoloniserande och kunskapsspridande funktion då den är skriven av en urfolksförfattare. / This undergraduate dissertation examines the various discourses surrounding the supernatural present in Eden Robinson’s novel Monkey Beach (2000) from a postcolonial perspective. The theoretical framework consists of Jo-Ann Episkenew’s Indigenous Storytelling, as well as Michail Bachtin’s concept of dialogism, with heteroglossia as its basis. These have been applied to the text to analyse how Robinson utilises characters to depict different epistemologies, and how they relate to the portrayal of the supernatural in the novel. The conclusion of this dissertation is that Monkey Beach is polyphonic in its portrayal of the various perspectives of the supernatural; these perspectives constitute different discourses, which are depicted through the characters. The novel does not take place in an autonomous fictional universe; it functions as a counter-discourse to previous discourses about Indigenous peoples in Canada, which gives it a decolonising and knowledge-disseminating function as it is written by an Indigenous author.

京都大学 / 新制・課程博士 / 博士(理学) / 甲第25142号 / 理博第5049号 / 新制||理||1719(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 中川 尚史, 教授 高橋 淑子, 准教授 中村 美知夫 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-03-04T19:04:18Z No. of bitstreams: 1 felipegomesduque.pdf: 1280593 bytes, checksum: 1f3d9c0ec3a41fa23d8f1844be3efc5c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-04-24T01:56:12Z (GMT) No. of bitstreams: 1 felipegomesduque.pdf: 1280593 bytes, checksum: 1f3d9c0ec3a41fa23d8f1844be3efc5c (MD5) / Made available in DSpace on 2016-04-24T01:56:12Z (GMT). No. of bitstreams: 1 felipegomesduque.pdf: 1280593 bytes, checksum: 1f3d9c0ec3a41fa23d8f1844be3efc5c (MD5) Previous issue date: 2016-07-19 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este trabalho apresenta um algoritmo baseado na técnica de otimização bio-inspirada denominada Monkey Search (MS) para alocação ótima de bancos de capacitores em sistemas de distribuição. O método proposto apresenta modificações e aprimoramentos da técnica MS para representar de forma adequada às características e restrições do problema de alocação de capacitores resultando em um novo algoritmo denominado Modified Monkey Search (MMS). O programa desenvolvido em MATLAB é utilizado para teste em diversos sistemas de distribuição. Os resultados obtidos apontam para um algoritmo com boa eficiência computacional. / This paper presents an algorithm based on bio-inspired optimization technique called Monkey Search (MS) for optimal allocation of capacitors in distribution systems. The proposed method presents modifications and enhancements of the MS technique to represent the characteristics and constraints of the problem related with capacitor allocation resulting in a new algorithm called Modified Monkey Search (MMS). The program developed in MATLAB is used to test multiple distribution systems. The results point to a computational efficient algorithm.

Malaria is one the world’s most devastating diseases. Several classes of drugs are used to treat malaria. Artemisinin combination therapy is the first line treatment of uncomplicated malaria. The artemisinin derivative, artemisone in conjunction with the Pheroid® drug delivery system, is the focus of this thesis. The impact of the Pheroid® on the bioavailability of artemisone was evaluated in vervet monkeys. The resulting artemisone plasma levels were much lower (Cmax of 47 and 114 ng/mL for reference and Pheroid® test formulations respectively) than expected for the dosages administered (60 mg/kg). The Pheroid® improved the pharmacokinetic profile of artemisone in a clinically significant manner. The metabolism of artemisone was assessed in vitro by using human and monkey liver and intestinal microsomes, and recombinant CYP3A4 enzymes. The Pheroid® inhibits the microsomal metabolism of artemisone. In addition, there is a species difference in artemisone metabolism between man and monkey since the in vitro intrinsic clearance of the reference formulation with monkey liver microsomes is ~8 fold higher in the monkey liver microsomes compared to the human liver microsomes and the estimated in vivo hepatic clearance for the monkey is almost twofold higher than in humans. Artemisone has potent antimalarial activity. Its in vitro efficacy was approximately twofold higher than that of either artesunate or dihydroartemisinin when evaluated against P. falciparum W2, D6, 7G8, TM90-C2B, TM91-C235 and TM93-C1088 parasite strains. The Pheroid® drug delivery system did not improve or inhibit the in vitro efficacy of artemisone or DHA. Artemisone (reference and Pheroid® test formulations) and metabolite M1 abruptly arrested the growth of P. falciparum W2 parasites and induced the formation of dormant ring stages in a manner similar to that of DHA. Interaction of artemisone with the p-glycoprotein (p-gp) efflux transporter was investigated. Artemisone stimulates ATPase activity in a concentration-dependent manner, whereas the Pheroid® inhibited this p-gp ATPase activity. P-gp ATPase activity stimulation was fourfold greater in human than cynomolgus monkey MDR1 expressed insect cell membranes. Artemisone alone and artemisone entrapped in Pheroid® vesicles showed moderate apical to basolateral and high basolateral to apical permeability (Papp) across Caco-2 cells. The Papp efflux ratio of artemisone and artemisone entrapped in Pheroid® vesicles were both >5, and decreased to ~1 when the p-gp inhibitor, verapamil, was added. Therefore, artemisone is a substrate for mammalian p-gp. The cytotoxic properties of Pheroid® on Caco-2 cells were assessed and the pro-Pheroid® seems to be non-toxic at concentrations of 1.25%. Vervet monkey plasma caused antibody-mediated growth inhibition of P. falciparum. Heat inactivated or protein A treatment proved useful in the elimination of the growth-inhibitory activity of the drug-free plasma. Plasma samples containing artemisone could not be analysed by the ex-vivo bioassay method. The dual labelling ROS assay did not prove to be useful in the evaluation of ROS production by artemisone and the Pheroid® delivery system. In conclusion, entrapment of artemisone in the Pheroid® delivery system improves the pharmacokinetic properties of artemisone, but does not improve or inhibit its antimalarial efficacy in vitro. The Pheroid® inhibited both the microsomal metabolism of artemisone and P-gp ATPase activity and was shown to be non-toxic at clinically usable concentrations. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Malaria is one the world’s most devastating diseases. Several classes of drugs are used to treat malaria. Artemisinin combination therapy is the first line treatment of uncomplicated malaria. The artemisinin derivative, artemisone in conjunction with the Pheroid® drug delivery system, is the focus of this thesis. The impact of the Pheroid® on the bioavailability of artemisone was evaluated in vervet monkeys. The resulting artemisone plasma levels were much lower (Cmax of 47 and 114 ng/mL for reference and Pheroid® test formulations respectively) than expected for the dosages administered (60 mg/kg). The Pheroid® improved the pharmacokinetic profile of artemisone in a clinically significant manner. The metabolism of artemisone was assessed in vitro by using human and monkey liver and intestinal microsomes, and recombinant CYP3A4 enzymes. The Pheroid® inhibits the microsomal metabolism of artemisone. In addition, there is a species difference in artemisone metabolism between man and monkey since the in vitro intrinsic clearance of the reference formulation with monkey liver microsomes is ~8 fold higher in the monkey liver microsomes compared to the human liver microsomes and the estimated in vivo hepatic clearance for the monkey is almost twofold higher than in humans. Artemisone has potent antimalarial activity. Its in vitro efficacy was approximately twofold higher than that of either artesunate or dihydroartemisinin when evaluated against P. falciparum W2, D6, 7G8, TM90-C2B, TM91-C235 and TM93-C1088 parasite strains. The Pheroid® drug delivery system did not improve or inhibit the in vitro efficacy of artemisone or DHA. Artemisone (reference and Pheroid® test formulations) and metabolite M1 abruptly arrested the growth of P. falciparum W2 parasites and induced the formation of dormant ring stages in a manner similar to that of DHA. Interaction of artemisone with the p-glycoprotein (p-gp) efflux transporter was investigated. Artemisone stimulates ATPase activity in a concentration-dependent manner, whereas the Pheroid® inhibited this p-gp ATPase activity. P-gp ATPase activity stimulation was fourfold greater in human than cynomolgus monkey MDR1 expressed insect cell membranes. Artemisone alone and artemisone entrapped in Pheroid® vesicles showed moderate apical to basolateral and high basolateral to apical permeability (Papp) across Caco-2 cells. The Papp efflux ratio of artemisone and artemisone entrapped in Pheroid® vesicles were both >5, and decreased to ~1 when the p-gp inhibitor, verapamil, was added. Therefore, artemisone is a substrate for mammalian p-gp. The cytotoxic properties of Pheroid® on Caco-2 cells were assessed and the pro-Pheroid® seems to be non-toxic at concentrations of 1.25%. Vervet monkey plasma caused antibody-mediated growth inhibition of P. falciparum. Heat inactivated or protein A treatment proved useful in the elimination of the growth-inhibitory activity of the drug-free plasma. Plasma samples containing artemisone could not be analysed by the ex-vivo bioassay method. The dual labelling ROS assay did not prove to be useful in the evaluation of ROS production by artemisone and the Pheroid® delivery system. In conclusion, entrapment of artemisone in the Pheroid® delivery system improves the pharmacokinetic properties of artemisone, but does not improve or inhibit its antimalarial efficacy in vitro. The Pheroid® inhibited both the microsomal metabolism of artemisone and P-gp ATPase activity and was shown to be non-toxic at clinically usable concentrations. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

This thesis details -in personal narrative form- the process by which the author directed a production of Elizabeth Wong's Amazing Adventures of the Marvelous Monkey King at Dr. Michael M. Krop Senior High School in Miami, Florida. The following text explains elements of pre-production, presents relevant research associated with the play, describes the production process in detail, and states conclusions drawn by the author about the experience. The work challenged both the ensemble and the director to seek new avenues of expression and theatricality different from those traditionally explored in their respective educational settings.