The \u3cem\u3emir-51\u3c/em\u3e Family of MicroRNAs Functions in Diverse Regulatory Pathways in \u3cem\u3eCaenorhbditis elegans\u3c/em\u3e

The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans

My Words Fly Up, My Thoughts Remain Below : Community and Penance in Early Modern English Drama

This dissertation examines the vexed relationship between Christian doctrine, practice, and community in English Renaissance drama due to the abandonment of the sacrament of auricular confession during the Protestant Reformation. I argue that many English Renaissance dramatists were sensitive to the vast ramifications of the Reformers\u27 theological understanding of penance, particularly in its emphasis upon a sinner\u27s ability to accomplish unmediated contrition, and to be psychologically and emotionally satisfied thereby. By desacramentalizing and interiorizing penitential practices, the Protestant understanding of penance fundamentally changed the ways in which communities dealt with sins. As this dissertation demonstrates, many of the plays from this period stage moments of penance that are problematic both for the repentant sinner and for the community in which the offender lives. Penitential practices are variously feigned, manipulated, perverted, or controlled by the state in many of these plays, often leading to the death of the penitent and the destruction of the community. The kneeling figure of the penitential Claudius in Shakespeare\u27sHamletexemplifies these representations of the struggle to accomplish repentance, and my dissertation proceeds to examine similar manifestations of these problems in the works of Campion, Marlowe, Beaumont and Fletcher, Middleton, Marston, Massinger, Webster, and Ford. The abruptness of the change in the religion of England would have inevitably caused great disruption in the people\u27s imaginative understanding of the sacred, and how an individual relates to the divine. I suggest that this disruption, particularly in the life of the community, was keenly felt by early modern English playwrights, and that they explore the problems relating to penance and the community in a wide variety of their plays

The Necessity and Possibility of the Use of the Principle of Generic Consistency by the UK Courts to Answer the Fundamental Questions of Convention Rights Interpretation

This thesis seeks to engage with and give answers to the fundamental question of rights interpretation confronting the British judiciary under the Human Rights Act 1998 (HRA). As a premise, it recognises that the textual openness and consequential semantic uncertainty of the requirements of the Convention rights necessitates their interpretation. In determining the approach the courts should apply, this thesis takes as its structural foundation an analysis of the current approach of the domestic courts and the European Court of Human Rights (ECtHR) to the five pivotal questions of interpretation: who has rights, the substantive nature of those rights, how rights are to be weighted and balanced in cases of conflict, whether they are rights under a will or an interest conception, and against whom the rights are held? From this basis, the thesis builds upon the existing knowledge to apply Alan Gewirth’s Principle of Generic Consistency (PGC) to the current judicial position, to critique its compatibility with this principle’s requirements. Through analysis of core settled characteristics of the Convention rights, the substance of the courts’ judgements and the ECtHR’s jurisprudence, and supported by both dialectically necessary and contingent arguments, it is ultimately argued that it is, theoretically and practically, both necessary and possible for the domestic courts to be guided by the PGC in their interpretive approach. Finally, an improved understanding of the principle of human dignity will be advocated as a means through which the domestic courts can apply the PGC’s requirements. By this means, this thesis ultimately proposes an interpretive approach to the Convention rights which gives compelling guidance in answering the fundamental questions of rights interpretation and, by encouraging direct principled engagement with these questions, increases the public understanding of the fundamental nature of rights and the acceptability of the HRA and judgements under it

"The home of the living writer" : the playwright and the Abbey Theatre

This thesis attempts to outline the practical relationship between Irish playwrights and the Abbey Theatre, from the early work of the Irish Literary Theatre in 1899, until the present day. It argues that the Abbey's reputation for being a writer's theatre tends to be contradicted by its distant association with Irish playwrights during the greater part of its history. Only during the early 1980s was there an active attempt to integrate the playwright within the company, creating a vibrant and active community for the development of new writing. Up until the 1980s the Abbey subscribed to the established twentieth-century view that the playwright was a literary writer, outside the creative centre of theatre. The Abbey's changing roles -- from literary theatre, to institutional national theatre and to director's theatre -- distracted the Theatre from acknowledging the valuable contribution individual dramatists could make, ensuring that the playwright remained vulnerable and isolated. The Abbey remained heavily dependent on its own historical inheritance and international reputation, satisfied with a repertoire of predictable classics. The Theatre's approach to playwrights changed in 1978, when Artistic Director Joe Dowling attempted to create what he termed `the home of the living writer'. With assistance from Script Editor Sean McCarthy, Dowling instigated a series of policies which went towards building a coherent writer's theatre within the Abbey, similar to London's Royal Court. Playwrights became members of the company, were assisted with the development of ideas and encouraged to contribute to the rehearsal process. These actions assured experimental playwright development, exemplified by the work of Tom MacIntyre, whose work proved that a playwright could evolve his own artistic identity within an established theatre

Imagined and imaginary whales: Benedict Anderson, Salman Rushdie and George Orwell

George Orwell, anticipating many of the arguments made by Benedict Anderson in the “Patriotism and Racism” chapter of Imagined Communities, illuminated patriotism and nationalism as shifting aspects of a wider dialectical interplay between an identification with imagined communities and a loyalty to humanity. Orwell's essay “Inside the Whale” can be seen, contrary to Salman Rushdie's criticism that it advocates quietism, as an essay about imaginary homelands. In this reading the whale is a metaphor for a dialectical space created by a writer in order to gain purchase on the unceasing dialectic of history. Analysis of The Lion and the Unicorn in this article links Orwell's work with that of Anderson and Rushdie by exploring in his vision of a classless England the relationship between the personal imaginary homeland and the political imagined community

Calculations of periodicity from H<i>α</i> profiles of Proxima Centauri

We investigate retrieval of the stellar rotation signal for Proxima Centauri. We make use of high-resolution spectra taken with UVES and HARPS of Proxima Centauri over a 13-yr period as well as photometric observations of Proxima Centauri from ASAS and HST. We measure the Hα equivalent width and Hα index, skewness and kurtosis and introduce a method that investigates the symmetry of the line, the peak ratio, which appears to return better results than the other measurements. Our investigations return a most significant period of 82.6 ± 0.1 days, confirming earlier photometric results and ruling out a more recent result of 116.6 days which we conclude to be an alias induced by the specific HARPS observation times. We conclude that whilst spectroscopic Hα measurements can be used for period recovery, in the case of Proxima Centauri the available photometric measurements are more reliable. We make 2D models of Proxima Centauri to generate simulated Hα, finding that reasonable distributions of plage and chromospheric features are able to reproduce the equivalent width variations in observed data and recover the rotation period, including after the addition of simulated noise and flares. However the 2D models used fail to generate the observed variety of line shapes measured by the peak ratio. We conclude that only 3D models which incorporate vertical motions in the chromosphere can achieve this

ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor

ERdj5 is a member of the protein disulfide isomerase family of proteins localized to the endoplasmic reticulum (ER) of mammalian cells. To date, only a limited number of substrates for ERdj5 are known. Here we identify a number of endogenous substrates that form mixed disulfides with ERdj5, greatly expanding its client repertoire. ERdj5 previously had been thought to exclusively reduce disulfides in proteins destined for dislocation to the cytosol for degradation. However, we demonstrate here that for one of the identified substrates, the low-density lipoprotein receptor (LDLR), ERdj5 is required not for degradation, but rather for efficient folding. Our results demonstrate that the crucial role of ERdj5 is to reduce non-native disulfides formed during productive folding and that this requirement is dependent on its interaction with BiP. Hence, ERdj5 acts as the ER reductase, both preparing misfolded proteins for degradation and catalyzing the folding of proteins that form obligatory non-native disulfides

Understanding the Forms and Trends of Capital Mobility from China into Ghana’s Agricultural Sector: From Neo-liberalism to Social Innovation

Given the fact that China has become the top investor in Ghana’s economy, this paper sought to interrogate the forms and trends of Chinese capital mobility into Ghana’s agricultural sector and explain their attractiveness within neo-liberal and social innovation contexts. Primary and secondary data were drawn from purposively selected state institutions and other actors in the agricultural sector. Using descriptive and constant comparative analytic strategies, we found out that the capital mobility from China into Ghana’s agricultural sector has been very visible and more attractive in trade but not in landed investment. It was further discovered that the forms and trends of the Chinese capital mobility would not have to be understood within neo-liberal persuasions such as trade liberalization and privatization alone but it would also have to be understood within the social innovative contexts of technological advancement and the organizational novelties upon which it is promoted and spread. We argue that the increasing rate of importation of agricultural inputs from China is an opportunity for knowledge transfer and technological adoption to aid the development of appropriate technology, but its sustenance would require the application of social innovative practices