12,448 research outputs found

    An exploration of the language within Ofsted reports and their influence on primary school performance in mathematics: a mixed methods critical discourse analysis

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    This thesis contributes to the understanding of the language of Ofsted reports, their similarity to one another and associations between different terms used within ‘areas for improvement’ sections and subsequent outcomes for pupils. The research responds to concerns from serving headteachers that Ofsted reports are overly similar, do not capture the unique story of their school, and are unhelpful for improvement. In seeking to answer ‘how similar are Ofsted reports’ the study uses two tools, a plagiarism detection software (Turnitin) and a discourse analysis tool (NVivo) to identify trends within and across a large corpus of reports. The approach is based on critical discourse analysis (Van Dijk, 2009; Fairclough, 1989) but shaped in the form of practitioner enquiry seeking power in the form of impact on pupils and practitioners, rather than a more traditional, sociological application of the method. The research found that in 2017, primary school section 5 Ofsted reports had more than half of their content exactly duplicated within other primary school inspection reports published that same year. Discourse analysis showed the quality assurance process overrode variables such as inspector designation, gender, or team size, leading to three distinct patterns of duplication: block duplication, self-referencing, and template writing. The most unique part of a report was found to be the ‘area for improvement’ section, which was tracked to externally verified outcomes for pupils using terms linked to ‘mathematics’. Those required to improve mathematics in their areas for improvement improved progress and attainment in mathematics significantly more than national rates. These findings indicate that there was a positive correlation between the inspection reporting process and a beneficial impact on pupil outcomes in mathematics, and that the significant similarity of one report to another had no bearing on the usefulness of the report for school improvement purposes within this corpus

    A Design Science Research Approach to Smart and Collaborative Urban Supply Networks

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    Urban supply networks are facing increasing demands and challenges and thus constitute a relevant field for research and practical development. Supply chain management holds enormous potential and relevance for society and everyday life as the flow of goods and information are important economic functions. Being a heterogeneous field, the literature base of supply chain management research is difficult to manage and navigate. Disruptive digital technologies and the implementation of cross-network information analysis and sharing drive the need for new organisational and technological approaches. Practical issues are manifold and include mega trends such as digital transformation, urbanisation, and environmental awareness. A promising approach to solving these problems is the realisation of smart and collaborative supply networks. The growth of artificial intelligence applications in recent years has led to a wide range of applications in a variety of domains. However, the potential of artificial intelligence utilisation in supply chain management has not yet been fully exploited. Similarly, value creation increasingly takes place in networked value creation cycles that have become continuously more collaborative, complex, and dynamic as interactions in business processes involving information technologies have become more intense. Following a design science research approach this cumulative thesis comprises the development and discussion of four artefacts for the analysis and advancement of smart and collaborative urban supply networks. This thesis aims to highlight the potential of artificial intelligence-based supply networks, to advance data-driven inter-organisational collaboration, and to improve last mile supply network sustainability. Based on thorough machine learning and systematic literature reviews, reference and system dynamics modelling, simulation, and qualitative empirical research, the artefacts provide a valuable contribution to research and practice

    Radical Left Parties and the Role of Euroscepticism

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    Globalization has shifted the political competition landscape in Western Europe. Extensive research has studied the impact of this on the radical right, yet little attention has been paid to the radical left. This dissertation, comprised of three papers, analyses the impact of the increased European integration emphasis on the radical left. My first paper analyses whether there is a beneficial policy position for the radical left on European integration. The chapter finds that there is an electoral benefit to a Eurosceptic position for radical left parties but also shows that this benefit is constrained when a Eurosceptic competitor, i.e. radical right party, enters the party system. My second paper follows from this and examines an alternative approach for the radical left on European integration. While the benefit of a Eurosceptic position can be constrained, blurring the position on European integration can help avoid losing pro-EU voters. The chapter finds that position blurring on EU integration is beneficial when there is electorate polarization but harmful when the electorate is in consensus on EU integration. When there is consensus, radical left parties benefit from a clear position on EU integration. My third paper is co-authored with Royce Carroll and zooms into the findings of the first two chapters by examining the demand side of Euroscepticism. The paper finds that European integration is an important issue for vote choice of the electorate. The results of the chapter show that the more Eurosceptic voters are, the higher their propensity to vote for a radical left party becomes. These three papers demonstrate how the issue of European integration is in the centre of radical left strategy from a supply and demand side perspective. This thesis contributes to the literature by providing a detailed understanding of the success of small parties beyond their issue ownership

    Proof of Concept of Therapeutic Gene Modulation of MBNL1/2 in Myotonic Dystrophy

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    La distrofia miotónica tipo 1 es una enfermedad genética rara multisistémica que afecta a 1 de cada 3000-8000 personas. La causa molecular de la enfermedad proviene de repeticiones tóxicas “CTG” en el gen DMPK (DM Protein Kinase). Tras la transcripción, estas repeticiones forman una estructura de horquilla que se une con alta afinidad a la familia de proteínas MBNL (Muscleblind-like) que agota su función de regulación de la poliadenilación y el splicing alternativo postranscripcional en numerosos transcritos. La pérdida de función de MBNL provoca una cascada de efectos posteriores, que eventualmente conducen a síntomas clínicos que incluyen miotonía, debilidad y atrofia muscular, cataratas, disfunción cardíaca y trastorno cognitivo. La restauración de la función de la proteína MBNL es clave para aliviar los síntomas debilitantes de esta enfermedad. Se han utilizado oligonucleótidos antisentido (AON) para apuntar a las repeticiones de DMPK y liberar MBNL del secuestro, lo que da como resultado resultados terapéuticos prometedores en modelos celulares y animales de la enfermedad. Otro factor que interviene en la pérdida de función de las proteínas MBNL son los miRNAs que regulan su traducción. Aquí se muestra el uso de AON dirigidos a la actividad de miR-23b y miR-218, que se ha demostrado previamente que regulan directamente MBNL1 y MBNL2. Estos antimiRs recibieron modificaciones FANA para aumentar su entrega en las células y reducir la toxicidad. También se probaron los AON, denominados blockmiRs, que se unen de manera complementaria a los sitios de unión confirmados de miR-23b y miR-218 en los 3'-UTR de las transcripciones de MBNL1 y MBNL2. De esta manera, los miRNAs no pueden unirse y regular la traducción de MBNL, lo que aumenta la cantidad de proteína MBNL producida en una célula deficiente. Aquí se propone el uso de AON de nuevo diseño dirigidos a la actividad de miR-23b y miR-218 para regular MBNL1 y MBNL2 a través de (1) exploración del bloqueo de miRNA a través de FANA-antimiR AON in vitro, (2) exploración del bloqueo del sitio de unión de miRNA a través de la estrategia blockmiR in vitro e in vivo con el uso de modificaciones químicas de LNA, y (3) mejora de la química de la estrategia blockmiR mediante el uso de tecnología de péptidos de penetración celular in vitro e in vivo.Myotonic Dystrophy Type 1 is a multi-systemic rare genetic disease affecting 1 in 3000-8000 people. The molecular cause of the disease stems from toxic “CTG” repetitions in the DMPK (DM Protein Kinase) gene. Upon transcription, these repetitions form a hairpin structure that binds with high affinity to the MBNL (Muscleblind-like) family of proteins depleting their function of post-transcriptional alternative splicing and polyadenylation regulation on numerous transcripts. MBNL loss-of-function causes a cascade of downstream effects, which eventually lead to clinical symptoms including myotonia, muscle weakness and atrophy, cataracts, cardiac dysfunction, and cognitive disorder. The restoration of MBNL protein function is key to relieving the debilitating symptoms of this disease. Antisense oligonucleotides (AONs) have been used to target the DMPK repeats and release MBNL from sequestration resulting in promising therapeutic results in cellular and animal models of the disease. Another factor playing a role in the loss-of-function of MBNL proteins are the miRNAs that regulate their translation. Here is shown the use of AONs targeting miR-23b and miR-218 activity, which have been previously shown to directly regulate MBNL1 and MBNL2. These antimiRs were given FANA modifications to increase their delivery in cells and lower toxicity. Also tested are AONs, termed blockmiRs, that complementary bind to the confirmed binding sites of miR-23b and miR-218 in the 3’-UTRs of MBNL1 and MBNL2 transcripts. In this way, the miRNAs are unable to bind and regulate the translation of MBNL thereby augmenting the amount of MBNL protein made in an otherwise deficient cell. Proposed here is the use of newly designed AONs targeting miR-23b and miR-218 activity in order to regulate MBNL1 and MBNL2 through (1) exploration of miRNA blocking through FANA-antimiR AONs in vitro, (2) exploration of miRNA binding site blocking through blockmiR strategy in vitro and in vivo with the use of LNA chemical modifications, and (3) improvement of the chemistry of the blockmiR strategy through the use of cell penetrating peptide technology in vitro and in vivo

    A correlation between tellurite resistance and nitric oxide detoxification in Salmonella Typhimurium

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    Salmonella are important enteric pathogens that are responsible for causing various diseases from gastroenteritis to systemic typhoid fever. Salmonella are a major contributor to morbidity and mortality worldwide. Crucial to their pathogenesis is the survival in harmful conditions elicited by the host immune system, one of these being reactive oxygen and nitrogen species (ROS/RNS). These are produced by macrophages and neutrophils in an attempt to eliminate pathogens. Salmonella, have the unique ability to colonise macrophages and have dedicated nitric oxide (NO) detoxification systems. There are three prominent metalloenzymes (HmpA, NorVW and NrfA) heavily researched in the literature for NO detoxification. Previous work suggested that more proteins are responsible for the nitrosative stress response with these being regulated by the nitric oxide sensitive transcriptional repressor, NsrR. This study demonstrates a relationship between three putative tellurite resistance proteins regulated by NsrR (STM1808, YeaR and TehB) and NO detoxification. A Functional redundancy between these proteins was observed for anaerobic protection against NO and tellurite. Furthermore, this study identified that proteins responsible in NO protection such as HmpA and YtfE also provide resistance to tellurite during aerobic and anaerobic conditions, respectively. Tellurite resistant Salmonella strains were evolved by continued passage in this study that consequently had altered H2O2 resistance profiles and increased sensitivity to antibiotics. However, these strains were not significantly attenuated during macrophage survival or during the presence of NO in vitro. Additionally, the hypothetical protein YgbA, which has predicted roles in NO detoxification, was found to be important to Salmonella survival in macrophages. However, in vitro NO exposure with the NO donor deta NONOate only showed a role for anaerobic protection
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