Le Syndrome de Taybi-Linder (TALS) est une maladie génétique rare affectant le développement embryonnaire, caractérisée par un nanisme microcéphalique sévère et un décès précoce des patients. Le gène muté dans ce syndrome est RNU4ATAC, qui encode un petit ARN nucléaire (snRNA) non-codant : U4atac. Ce snRNA est l’une des briques composant le spliceosome mineur, une machinerie nucléaire dédiée à l’épissage des introns U12, un groupe d’introns peu étudié car présent dans ~1 % des gènes seulement. Dans le TALS, ces introns sont fréquemment retenus dans les transcrits matures, l’épissage correct des introns U12 semble donc capital pour le développement embryonnaire. L’étude du profil transcriptomique des patients TALS permet ainsi d’établir les conséquences moléculaires d’un dysfonctionnement du spliceosome mineur, nous permettant d’en apprendre davantage sur les mécanismes d’épissage des introns U12 en condition physiologique ou pathologique, et sur le rôle de l’épissage mineur dans le développement embryonnaire. Cette thèse présente la première analyse approfondie du transcriptome de cellules provenant de patients TALS. Pour mener cette analyse, nous avons développé un pipeline bioinformatique qui, à partir de données RNA-seq de seconde génération, utilise différentes méthodes dédiées à l’étude différentielle de l’expression des gènes ou de la qualité d’épissage entre patients et contrôles. L’épissage étant particulièrement complexe à analyser à partir de reads courts, deux approches complémentaires ont été utilisées : l’une classique, basée sur l’alignement des reads, et l’autre plus originale, basée sur l’assemblage des reads et permettant de détecter plus d’événements d’épissage non-annotés (KisSplice). Une des conséquences attendue d’un dysfonctionnement du spliceosome mineur est une rétention massive des introns U12 dans les ARN matures. Cependant, la détection et la quantification de rétentions d’intron chez les mammifères constituent encore aujourd’hui un challenge bioinformatique. Nous avons donc utilisé une méthode récente dédiée à l’analyse des rétentions d’introns pour caractériser le plus précisément possible le profil transcriptomique des patients TALS. J’ai ainsi participé au développement de KisSplice et de notre outil d’analyse statistique des différentielles d’épissage, kissDE, et mis en évidence certaines caractéristiques de l’épissage mineur, que ce soit en condition physiologique ou pathologique / The Taybi-Linder Syndrome (TALS) is a rare genetic disorder of the embryonic development leading to a severe microcephaly, a primordial dwarfism and an early/unexpected death. The mutated gene in this syndrome is RNU4ATAC, which encode a non-coding small nuclear RNA (snRNA) named U4atac, involved in the minor spliceosome. This nuclear machinery is dedicated to the splicing of a small number of particular introns : the U12 introns. Because only about 1 % of the Human’s genes display at least one U12 intron, they have not been extensively study and little is known about their function. In TALS patients’ cells, most of the U12 introns are retained in mature transcripts ; hence, splicing of U12 introns seems important for the embryonic development. Studying TALS patients’ cells transcriptomes both in physiological and pathological conditions should enable us to precisely identify most of the molecular consequences of a minor splicing defect and could shed light on the mechanism linking minor splicing and embryonic development. This thesis is the first work to conduct an in depth analysis of TALS patients’ cells transcriptomes. In order to do a precise analysis, we developed a bioinformatic pipeline that uses multiple methods to detect differentially expressed or spliced genes between patients and controls and from second generation RNA-seq data. Splicing analysis is a very complex task complete with short reads ; hence, we used two complementary approaches. The first one is based on reads alignement to a reference genome, method conventionnally used to work on splicing, and the second one is based on reads assembly (KisSplice), a original method enabling to find more non-annotated splicing events. One of the expected consequences of a minor splicing malfunction is a global U12 introns retention in mature transcripts. However, intron retention detection and quantification in mammals is particulary difficult task in mammals, thus we used a new method dedicated to intron retentions analysis to study the transcriptomic profile of TALS patients. During my thesis, I was one of the developer of KisSplice and kissDE, our differential splicing analysis tool, and I identified important charcteristics of minor splicing either in physiological or pathological conditions

Bacteriophage MooMoo is a temperate phage that was isolated and propagated on Mycobacterium smegmatis (M. smeg). It typically produces turbid plaques, however spontaneous clear plaque mutants can be readily isolated. Both turbid (MooMoo-T) and clear plaque (MooMoo-C) formers can establish stable lysogens, but the parental turbid plaque forming phage has a higher lysogenic frequency. The phage repressor protein typically plays the central role in regulating the lysis/lysogeny decision. Therefore, we expected that the mutation responsible for the clear plaque phenotype would be located in the repressor gene. Remarkably, whole genome sequencing detected a single base pair mutation in the minor tail protein gene (gp19). The regulatory role of the repressor protein could not be excluded considering it was unclear how the mutation in gp19 was leading to the altered plaque phenotype. To locate the phage repressor, we used bioinformatics to identify several candidate genes with helix-turn-helix and DNA binding motifs (gp42, gp43 and gp44). We also cloned the parental and mutant gp19 genes. Each candidate gene was cloned into a shuttle vector. The clones of gp43, gp44 and both derivatives of gp19 did not prevent MooMoo growth, whereas the clones of gp42 inhibited phage growth. Based on these results, we concluded that gp42 is the phage repressor for MooMoo. To determine if the presence of gp19 alters lysogenic frequency, lysogeny assays of wild-type (WT) and mutant gp19 clones were evaluated. Compared to the MooMoo-C lysate, the cloned copy of the mutant gp19 showed a slight increase in lysogeny efficiency. The lysogeny frequencies on strains that carry cloned copies of gp19 (WT or mutant) were similar to those obtained on strains that lacked the plasmids. From these results, we concluded, the presence of either parental or mutant gp19 clones does not affect the lysogeny frequency. To determine if host cell physiology was affected by lysogeny, carbon, nitrogen, phosphorus and sulfur utilization resources were screened using high-throughput phenotypic microarrays. From these results, we concluded the presence of the WT or mutant prophage had no significant effect on the utilization of the resources tested.

Domestic Minor Sex Trafficking (DMST) affects hundreds of thousands of youth every year. In the past, DMST youth were often viewed by law enforcement and the criminal justice system as "offenders" and were usually arrested for solicitation even though they were minors. While new laws have begun to identify youth as victims, it has not yet been ensured that social workers have adopted this perspective. This quantitative study's purpose was to examine Cal State University San Bernardino (CSUSB) Bachelor of Social Work (BASW) and Master of Social Work (MSW) students' attitudes toward DMST youth. Participants completed an online questionnaire using Qualtrics software. Data were analyzed using SPSS version 21, using statistical tests including frequencies, Pearson's R, and ANOVA. The hypothesis that knowledge, exposure to curriculum, and past experiences impacted students' stigmatization of DMST youth was not supported by the data. Instead, results indicated that CSUSB social work students did not stigmatize the DMST population. Because these findings cannot be generalized to social workers in the field, future research should explore whether social workers currently working with DMST youth stigmatize this population. These findings also have implications for the CSUSB School of Social Work as they revealed that some students lacked education about this population and, consequently, felt unprepared to work with this population.

Major depressive disorder (MDD) is a debilitating disorder characterized by significant mood disturbance. In laboratory studies, MDD has been characterized by both blunted positive (PER) and negative emotional reactivity (NER). However, mood disordered persons' emotional reactivity has rarely been studied in naturalistic settings, and it is unknown how less severe forms of depression relate to emotional reactivity. To address these issues, the current study utilized two naturalistic sampling methods (the Day Reconstruction Method and the Experience Sampling Method) to examine PER and NER to daily life events in 35 individuals currently experiencing a major depressive episode (MDD), 26 individuals currently experiencing a minor depressive episode (mD), and 38 healthy controls. Both methods demonstrated that individuals with major and minor depression exhibited blunted PER relative to controls. In surprising contrast to previous laboratory findings, both individuals with MDD and mD showed increased NER relative to controls. Correlational analyses with severity measures indicated that depression and anxiety severity were positively related to NER and negatively related to PER. Findings suggest that NER in mood disorders may diverge as a function of assessment context and may be heightened in naturalistic environments. Despite the fact that mD is a milder mood disorder, findings suggest that mD results in similar emotional impairments as found in MDD.

This thesis analyses yearly mark-recapture-recovery information collected over a 36- year period, from 1968 to 2003, for 23 686 flipper-banded Little Penguins Eudyptula minor of Phillip Island, in south-eastern Australia. Such a long-term data set is extremely rare for any species. Few studies of any animal have been able to model age dependence for the survival, recapture and recovery probabilities simultaneously. I successfully apply such a modelling scheme and obtain biologically realistic age structures for the parameters. I also provide illustrations of erroneous results that may arise when analyses fail to consider simultaneous age dependence, or fail to detect annual variations that may mask age dependence. I obtain a low survival estimate of 17% in the first year of life, increasing to 71% in the second year, and around 80% thereafter, and declining gradually after age nine years. First-year survival increases with number of chicks fledged per pair, increases with annual average fledging weight and decreases with mean laying date. An increase in first-year survival is associated with warmer sea surface temperatures in the summer and autumn of the previous year, which agrees with biological considerations. Irrespective of this inter-year variation, birds born early in the breeding season, relative to the rest of their cohort, have greatly enhanced first-year survival, when compared to birds born late in that season. Fledglings survive better in years in which the mean fledgling weight is higher, and fledglings of above average weight have a better chance of survival than their underweight counterparts. I next analyse seven years of recapture data from a separate experiment studying the effect of banding on adult Little Penguins. In the year following marking, the i survival probability of banded birds is 6% lower than that of unbanded birds, while in subsequent years the survival is 4% lower for banded birds. Band loss is negligible. Finally, I compare the survival estimates for Phillip Island with those obtained for a six-year study in New Zealand. While first-year survival is significantly higher for New Zealand, there is a marked decline over time, coinciding with an increase in population size.

Bibliography: p. 726-753. / 2 v. (753 p. ; [551] p.) : music ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Elder School of Music

Abstract This thesis offers the first detailed critical account of the Greek-Australian writer, Alex Doucas (1900-1962) who came to Australia in 1927 as a migrant from Asia Minor. It attempts to place his work in the perspectives of Greek and Australian literatures and to evaluate his position both as a migrant and as a writer. The Asia Minor Catastrophe and the exchange of populations between Greece and Turkey in 1923, as well as the Great Depression he faced in Australia along with many other Australians had a profound effect on his social outlook. Considered one of the pioneers of Greek-Australian Literature, Doucas played an important role in the development of Greek community life in Australia during the pre- and post-World War II periods. His work consists of two published novels (one posthumously) and a significant body of published and unpublished, stories, poems, translations and essays. Out of print for some decades, it remains largely unknown to the general public or even to academic circles in Greece and in Australia. It was, however, a landmark of Greek-Australian Literature and continues to have more than historical interest in its treatment of migration, exile and displacement, and in its use of intercultural perspectives to forge a positive vision for humanity. Although forced into ill-paid manual labour for much of his life after his arrival in Australia, Alex Doucas tried to develop links and relationships with Australian intellectual circles and to become involved in Australian life in the broadest way. At the same time, he never lost contact with social, political and literary developments in Greece. Alex Doucas maintained close relations with both the Greek and Australian literary traditions. As a writer he belongs to the Greek generation of the 1930s and its literary traditions. In his work, he dealt with events which took place in Anatolia before the Asia Minor Catastrophe as well as with the impact the catastrophe had on Greek society. He is one of the first writers of his generation who turned his attention to the “other side of the coin” and investigated the impact of the Catastrophe on the Turkish people. This perspective was adopted mainly due to the openness that he found in Australia, an openness that led to Multiculturalism. Alex Doucas was a multiculturalist before his time. His work is a fine example of the Australian version of Multiculturalism. Through his brother Stratis Doucas (also a writer) and others, he kept himself informed on all sorts of changes and developments in his native country, Greece, especially as it was shaped after the Asia Minor Catastrophe. At the same time, he tried to understand the Australian way of life, its culture and its literary traditions. His bi-cultural position gave him a powerful perspective. He attempted to understand the Australian way of life through his Greekness and to find answers for problematic events that happened in Greece through his Australian experience. Across the entire span of Doucas’s work, it is clear that his political philosophy and his belief in the goals of socialism played a crucial role in his consciousness of himself as a writer whose role was to provide the artistic equivalent of the philosophical basis of Marxism, best expressed in the Theses on Feuerbach (1845) by Marx, in his famous dictum, "Philosophers have hitherto only interpreted the world in various ways; the point is to change it". In other words, it was never enough for Doucas simply to describe in social realist terms the conditions of life and the aspirations of human beings. His aim was to show how these conditions might be changed for the better, not only for the individual, but for the community as a whole. Equally, he wished to show how people’s aspirations, particularly those of an immigrant community familiar with exile, suffering and loss, might be more fully realised.

This thesis examines the motives, methods and successes of opposition to C. Julius Caesar in the period 60-50 leading to the outbreak of civil war in 49. An attempt has been made to distinguish between traditional and innovative methods of opposition. An evaluation of creativity levels and the social acceptability of actions has been conducted in an effort to understand adherence to moral standards in the pre-war period. In Chapter 2, opposition to Caesar in 60 and 59 is examined and found to be fierce, persistent and, despite Caesar ultimately achieving his aims, successful in a limited way. Chapter 3 examines the circumstances of 58-57. Caesar’s position was more firmly secured through the agency of Clodius’ tribunate, during which Cicero was exiled and Cato was removed from the political scene for both political and personal reasons. Examination of opposition to Caesar in Chapter 4 focuses on the period 56-54. It is demonstrated that prior to the conferences of Luca and Ravenna, opposition to Caesar was broadly undertaken by groups or individuals who fomented dissent between Crassus and Pompey in order to undermine the triumvirate as a whole. In 55 opposition to Caesar was nullified by a renewal of the triumvirate. In 54 opposition was resurgent and dominated the courts with limited success. In Chapter 5, opposition to Caesar in the period 53-50 is examined and is shown to be marked by anarchy, attempted reforms and the disintegration of the triumviral alliance. Given widespread impressions of pressure, corruption, violence and breakdown, especially in modern accounts of the period, it is suprising to discover that tactics used by Caesar’s opponents were traditional and socially acceptable for the most part, despite vehement political and personal disagreement. The will of the people was still respected by Caesar’s opponents; popular opinion in 59 was in fact the cause of opposition failure. While the Republic had suffered civil war in the opening decades of the first century BC, the state had resumed constitutional operation prior to 60. Traditional moral values and methods of gaining rank and prestige were still important and continued to be adhered to after 60. Methods of influence and social communication remained largely unchanged in the 50s, and ensured the continuity of political exchange without substantial innovation. From 56 to 54 opposition methods were opportunistic, a result of the renewal of the triumvirate. Caesar’s opponents continued to adhere to traditional political practice, despite dominance of the political machinary by the triumvirate. In 54 Caesar’s opponents gained control of the law courts, which resulted in numerous trials but no break with traditional or socially acceptable behaviour. Opposition between 53 and 50 remained traditional in most cases within an environment marked by anarchy and political stalemate, fueled by the intransigence of Caesar and Pompey who refused to recognise each others’ dignitas. The Civil War, then, was not caused by an extended period of constitutional instability. The Civil War was the result of political deadlock at the end of the 50s, motivated by the social and political inflexibility of a small group of Senators.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.