4,143 research outputs found

    Long-Molecule Assessment of Ribosomal DNA and RNA

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    The genes encoding ribosomal RNA and their transcriptional products are essential for life, however, remain poorly understood. Even with the advent of long-range sequencing methodologies, rDNA loci are difficult to study and remain obscure, prompting the consideration of alternative methods to probing this critical region of the genome. The research outlined in this thesis utilises molecular combing, a fibre stretching technique, to isolate DNA molecules measuring more than 5 Mbp in length. The capture of DNA molecules of this size should assist in exploring the architecture of entire rDNA clusters at the single-molecule level. Combining molecular combing with SNP targeting probes, this study aims to distinguish and assess the arrangement of rDNA promoter variants which have been shown to exhibit dramatically different environmental sensitivity. Additionally, through the application of Oxford Nanopore Technologies direct RNA sequencing, the work here has demonstrated the capture of near full-length rRNA primary transcripts, which will allow for assessing post-transcriptional modification across the length of multiple coding subunits within a single molecule, for the first time. Furthermore, an exploration of RNA modification profiles across sample types representative of different developmental stages has been conducted. This study predicts many sites to be differentially modified across these different developmental conditions, several of which are known to be important for, if not crucial in ribosome biogenesis and function. The work outlined in this thesis provides a framework for future studies to conduct long-molecule, genetic, and epitranscriptome profiling of this vital region of the genome, and its dynamic response to a changing environment

    A Critical Review Of Post-Secondary Education Writing During A 21st Century Education Revolution

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    Educational materials are effective instruments which provide information and report new discoveries uncovered by researchers in specific areas of academia. Higher education, like other education institutions, rely on instructional materials to inform its practice of educating adult learners. In post-secondary education, developmental English programs are tasked with meeting the needs of dynamic populations, thus there is a continuous need for research in this area to support its changing landscape. However, the majority of scholarly thought in this area centers on K-12 reading and writing. This paucity presents a phenomenon to the post-secondary community. This research study uses a qualitative content analysis to examine peer-reviewed journals from 2003-2017, developmental online websites, and a government issued document directed toward reforming post-secondary developmental education programs. These highly relevant sources aid educators in discovering informational support to apply best practices for student success. Developmental education serves the purpose of addressing literacy gaps for students transitioning to college-level work. The findings here illuminate the dearth of material offered to developmental educators. This study suggests the field of literacy research is fragmented and highlights an apparent blind spot in scholarly literature with regard to English writing instruction. This poses a quandary for post-secondary literacy researchers in the 21st century and establishes the necessity for the literacy research community to commit future scholarship toward equipping college educators teaching writing instruction to underprepared adult learners

    Annual Report 2022

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    Cardiovascular Dysfunction and the ATP-Adenosine Axis in Trauma

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    Introduction Trauma is a significant contributor to global mortality and morbidity. Outcomes have improved over the last several decades, but there are still a population of patients who die after surviving their initial injuries. The cardiovascular system is vulnerable to the effects of both shock and inflammation but has not been adequately investigated. The purines ATP and adenosine have critical roles in metabolism, immunity, and the regulation of the cardiovascular system and may be pivotal in understanding why patients still die. Methods A retrospective analysis was used to describe the population with cardiovascular dysfunction. A prospective study design was used in the measurement of ATP and adenosine. Proteomic analysis was performed on samples from a prospectively maintained trauma biobank. Results Cardiovascular dysfunction was the dominant organ system to develop dysfunction following trauma and occurred in one third of trauma patients admitted to critical care. It was associated with a significant mortality and was manifest early in the disease process. ATP was associated with organ dysfunction; however, adenosine did not show any relationship to clinical outcome in this study. Proteomic analysis identified three distinct proteins that were upregulated in CVD; K2013, ATPase WRNIP1, and heat shock 70 kDa protein. K2013 has not yet been characterised and may be a novel biomarker of cardiovascular pathology. The role of heat shock 70 kDa protein in cardiovascular pathology has been documented in other pathologies, but this the first time it has been associated with cardiovascular dysfunction in trauma. 5 Conclusion Cardiovascular dysfunction is a phenotype of organ dysfunction that has not been fully described in the literature. It is associated with poor clinical outcomes, and can be predicted early. The ATP-adenosine axis did not influence the development of cardiovascular dysfunction. There was a distinct pattern of protein upregulation that differentiated patients who developed cardiovascular dysfunction

    Enhancing the Structural Stability of α-phase Hybrid Perovskite Films through Defect Engineering Approaches under Ambient Conditions

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    This thesis investigates methods whereby perovskite solar cell power conversion efficiency and material stability may be improved. Hybrid perovskites have gained increased attention for optoelectronic applications due to favourable properties such as strong absorption, facile processing, and changeable band-gap. Despite excellent improvements in power conversion efficiency of devices, perovskite films are unstable, degrading with relative ease in the presence of moisture, oxygen, light, heat, and electric fields. The focus of this thesis is on ambient atmosphere stability, concerned with the influence of moisture in particular on perovskite film fabrication, degradation, and device functionality. In order to shed light on the impact of ambient atmosphere on perovskite films, experiments are designed to investigate films during fabrication and degradation. The influences firstly of stoichiometry during ambient fabrication, and then ionic substitution (with caesium and formadinium) upon moisture-induced degradation are investigated. Finally, films and devices with a novel composition incorporating Zn are fabricated under ambient conditions to investigate the effect of Zn addition on perovskite film stability

    Financial and Economic Review 22.

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    How did Britain come to this? A century of systemic failures of governance

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    If every system is perfectly designed to get the results it gets, what is wrong with the design of the systems that govern Britain? And how have they resulted in failures in housing, privatisation, outsourcing, education and healthcare? In How Did Britain Come to This? Gwyn Bevan examines a century of varieties of systemic failures in the British state. The book begins and ends by showing how systems of governance explain scandals in NHS hospitals, and the failures and successes of the UK and Germany in responding to Covid-19 before and after vaccines became available. The book compares geographical fault lines and inequalities in Britain with those that have developed in other European countries and argues that the causes of Britain’s entrenched inequalities are consequences of shifts in systems of governance over the past century. Clement Attlee’s postwar government aimed to remedy the failings of the prewar minimal state, while Margaret Thatcher’s governments in the 1980s in turn sought to remedy the failings of Attlee’s planned state by developing the marketised state, which morphed into the financialised state we see today. This analysis highlights the urgent need for a new political settlement of an enabling state that tackles current systemic weaknesses from market failures and over-centralisation. This book offers an accessible, analytic account of government failures of the past century, and is essential reading for anyone who wants to make an informed contribution to what an innovative, capable state might look like in a post-pandemic world

    Deriving a mathematical framework for data-driven analyses of immune cell dynamics

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    Zelluläre Entscheidungen, wie z. B. die Differenzierung von T-Helferzellen (Th-Zellen) in spezialisierte Effektorlinien, haben großen Einfluss auf die Spezifität von Immunreaktionen. Solche Reaktionen sind das Ergebnis eines komplexen Zusammenspiels einzelner Zellen, die über kleine Signalmoleküle, so genannte Zytokine, kommunizieren. Die hohe Anzahl der Komponenten, sowie deren komplizierte und oft nichtlineare Interaktionen erschweren dabei die Vorhersage, wie bestimmte zelluläre Reaktionen erzeugt werden. Aus diesem Grund sind die globalen Auswirkungen der gezielten Beeinflussung einzelner Zellen oder spezifischer Signalwege nur unzureichend verstanden. So wirken beispielsweise etablierte Behandlungen von Autoimmunkrankheiten oft nur bei einem Teil der Patienten. Durch Einzelzellmethoden wie Live-Cell-Imaging, Massenzytometrie und Einzelzellsequenzierung, können Immunzellen heutzutage quantitativ auf mehreren Ebenen charakterisiert werden. Diese Ansammlung quantitativer Daten erlaubt die Formulierung datengetriebener Modelle zur Vorhersage von zellulären Entscheidungen, allerdings fehlen in vielen Fällen Methoden, um die verschiedenen Daten auf geeignete Weise zu integrieren und zu annotieren. Die vorliegende Arbeit befasst sich mit quantitativen Modellformulierungen für die Entscheidungsfindung von Zellen im Immunsystem mit dem Schwerpunkt auf Lymphozytenproliferation, -differenzierung und -tod.Cellular decisions, such as the differentiation of T helper (Th) cells into specialized effector lineages, largely impact the direction of immune responses. Such population-level responses are the result of a complex interplay of individual cells which communicate via small signaling molecules called cytokines. The system's complexity, stemming not only from the number of components but also from their intricate and oftentimes non-linear interactions, makes it difficult to develop intuition for how cellular responses are actually generated. Not surprisingly, the global effects of targeting individual cells or specific signaling pathways through perturbations are poorly understood. For instance, common treatments of autoimmune diseases often work for some patients, but not for others. Recently developed methods such as live-cell imaging, mass cytometry and single-cell sequencing now enable quantitative characterization of individual immune cells. This accumulating wealth of quantitative data has laid the basis to derive predictive, data-driven models of immune cell behavior, but in many cases, methods to integrate and annotate the data in a way suitable for model formulation are missing. In this thesis, quantitative workflows and methods are introduced that allow to formulate data-driven models of immune cell decision-making with a particular focus on lymphocyte proliferation, differentiation and death
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