13,735 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

    The Viability and Potential Consequences of IoT-Based Ransomware

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    With the increased threat of ransomware and the substantial growth of the Internet of Things (IoT) market, there is significant motivation for attackers to carry out IoT-based ransomware campaigns. In this thesis, the viability of such malware is tested. As part of this work, various techniques that could be used by ransomware developers to attack commercial IoT devices were explored. First, methods that attackers could use to communicate with the victim were examined, such that a ransom note was able to be reliably sent to a victim. Next, the viability of using "bricking" as a method of ransom was evaluated, such that devices could be remotely disabled unless the victim makes a payment to the attacker. Research was then performed to ascertain whether it was possible to remotely gain persistence on IoT devices, which would improve the efficacy of existing ransomware methods, and provide opportunities for more advanced ransomware to be created. Finally, after successfully identifying a number of persistence techniques, the viability of privacy-invasion based ransomware was analysed. For each assessed technique, proofs of concept were developed. A range of devices -- with various intended purposes, such as routers, cameras and phones -- were used to test the viability of these proofs of concept. To test communication hijacking, devices' "channels of communication" -- such as web services and embedded screens -- were identified, then hijacked to display custom ransom notes. During the analysis of bricking-based ransomware, a working proof of concept was created, which was then able to remotely brick five IoT devices. After analysing the storage design of an assortment of IoT devices, six different persistence techniques were identified, which were then successfully tested on four devices, such that malicious filesystem modifications would be retained after the device was rebooted. When researching privacy-invasion based ransomware, several methods were created to extract information from data sources that can be commonly found on IoT devices, such as nearby WiFi signals, images from cameras, or audio from microphones. These were successfully implemented in a test environment such that ransomable data could be extracted, processed, and stored for later use to blackmail the victim. Overall, IoT-based ransomware has not only been shown to be viable but also highly damaging to both IoT devices and their users. While the use of IoT-ransomware is still very uncommon "in the wild", the techniques demonstrated within this work highlight an urgent need to improve the security of IoT devices to avoid the risk of IoT-based ransomware causing havoc in our society. Finally, during the development of these proofs of concept, a number of potential countermeasures were identified, which can be used to limit the effectiveness of the attacking techniques discovered in this PhD research

    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

    Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions

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    Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and Wängberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms. Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 μg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis. Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1 1.1 Welcome to the anthropocene .......................................................................... 1 1.2 From cellular stress responses to ecosystem resilience ................................... 3 1.2.1 The individual pursuit for homeostasis ....................................................... 3 1.2.2 Stability from diversity ................................................................................. 5 1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical pollution? ................................................................................................................. 6 1.4 Functional ecotoxicological assessment of microbial communities ................... 9 1.5 Molecular tools – the key to a mechanistic understanding of stressor effects from a functional perspective in microbial communities? ...................................... 12 2. Aims and Hypothesis ......................................................................................... 14 2.1 Research question .......................................................................................... 14 2.2 Hypothesis and outline .................................................................................... 15 2.3 Experimental approach & concept .................................................................. 16 2.3.1 Aquatic freshwater biofilms as model community ..................................... 16 2.3.2 Diuron as model herbicide ........................................................................ 17 2.3.3 Experimental design ................................................................................. 18 3. Structural and physiological changes in microbial communities after chronic exposure - PICT and altered functional capacity ................................................. 21 3.1 Introduction ..................................................................................................... 21 3.2 Methods .......................................................................................................... 23 3.2.1 Biofilm cultivation ...................................................................................... 23 3.2.2 Dry weight and autotrophic index ............................................................. 23 3.2.4 Pigment analysis of periphyton ................................................................. 23 3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24 3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24 3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26 3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27 3.2.5 Community oxygen metabolism measurements ....................................... 28 3.3 Results and discussion ................................................................................... 29 3.3.1 Comparison of the structural community parameters ............................... 29 3.3.2 Photosynthetic activity and primary production of the communities after selection phase ................................................................................................. 33 3.3.3 Acquisition of photosynthetic tolerance .................................................... 34 3.3.4 Primary production at exposure conditions ............................................... 36 3.3.5 Tolerance detection in primary production ................................................ 37 3.4 Summary and Conclusion ........................................................................... 40 4. Community gene expression analysis by meta-transcriptomics ................... 41 4.1 Introduction to meta-transcriptomics ............................................................... 41 4.2. Methods ......................................................................................................... 43 4.2.1 Sampling and RNA extraction................................................................... 43 4.2.2 RNA sequencing analysis ......................................................................... 44 4.2.3 Data assembly and processing................................................................. 45 4.2.4 Prioritization of contigs and annotation ..................................................... 47 4.2.5 Sensitivity analysis of biological processes .............................................. 48 4.3 Results and discussion ................................................................................... 48 4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49 4.3.2 Insights into community stress response mechanisms using trend analysis (DRomic’s) ......................................................................................................... 51 4.3.3 Response pattern in the isoform PS genes .............................................. 63 4.5 Summary and conclusion ................................................................................ 65 5. Community metabolome analysis ..................................................................... 66 5.1 Introduction to community metabolomics ........................................................ 66 5.2 Methods .......................................................................................................... 68 5.2.1 Sampling, metabolite extraction and derivatisation................................... 68 5.2.2 GC-TOF-MS analysis ............................................................................... 69 5.2.3 Data processing and statistical analysis ................................................... 69 5.3 Results and discussion ................................................................................... 70 5.3.1 Characterization of the metabolic fingerprints .......................................... 70 5.3.2 Difference in the metabolic fingerprints .................................................... 71 5.3.3 Differential metabolic responses of the communities to short-term exposure of diuron ............................................................................................................ 73 5.4 Summary and conclusion ................................................................................ 78 6. Synthesis ............................................................................................................. 79 6.1 Approaches and challenges for linking molecular data to functional measurements ...................................................................................................... 79 6.2 Methods .......................................................................................................... 83 6.2.1 Summary on the data ............................................................................... 83 6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83 6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83 6.3 Results and discussion ................................................................................... 85 6.3.1 Results of aggregation techniques ........................................................... 85 6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86 6.3.3 Mechanistic view of the molecular stress responses based on KEGG functions ............................................................................................................ 89 6.4 Consolidation of the results – holistic interpretation and discussion ............... 93 6.4.1 Adaptation to chronic diuron exposure - from molecular changes to community effects.............................................................................................. 93 6.4.2 Assessment of the ecological costs of Pollution-induced community tolerance based on primary production ............................................................. 94 6.5 Outlook ............................................................................................................ 9

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    Classification of annotation semirings over containment of conjunctive queries

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    Funding: This work is supported under SOCIAM: The Theory and Practice of Social Machines, a project funded by the UK Engineering and Physical Sciences Research Council (EPSRC) under grant number EP/J017728/1. This work was also supported by FET-Open Project FoX, grant agreement 233599; EPSRC grants EP/F028288/1, G049165 and J015377; and the Laboratory for Foundations of Computer Science.We study the problem of query containment of conjunctive queries over annotated databases. Annotations are typically attached to tuples and represent metadata, such as probability, multiplicity, comments, or provenance. It is usually assumed that annotations are drawn from a commutative semiring. Such databases pose new challenges in query optimization, since many related fundamental tasks, such as query containment, have to be reconsidered in the presence of propagation of annotations. We axiomatize several classes of semirings for each of which containment of conjunctive queries is equivalent to existence of a particular type of homomorphism. For each of these types, we also specify all semirings for which existence of a corresponding homomorphism is a sufficient (or necessary) condition for the containment. We develop new decision procedures for containment for some semirings which are not in any of these classes. This generalizes and systematizes previous approaches.PostprintPeer reviewe

    Targeting Fusion Proteins of HIV-1 and SARS-CoV-2

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    Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.</p

    Data-to-text generation with neural planning

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    In this thesis, we consider the task of data-to-text generation, which takes non-linguistic structures as input and produces textual output. The inputs can take the form of database tables, spreadsheets, charts, and so on. The main application of data-to-text generation is to present information in a textual format which makes it accessible to a layperson who may otherwise find it problematic to understand numerical figures. The task can also automate routine document generation jobs, thus improving human efficiency. We focus on generating long-form text, i.e., documents with multiple paragraphs. Recent approaches to data-to-text generation have adopted the very successful encoder-decoder architecture or its variants. These models generate fluent (but often imprecise) text and perform quite poorly at selecting appropriate content and ordering it coherently. This thesis focuses on overcoming these issues by integrating content planning with neural models. We hypothesize data-to-text generation will benefit from explicit planning, which manifests itself in (a) micro planning, (b) latent entity planning, and (c) macro planning. Throughout this thesis, we assume the input to our generator are tables (with records) in the sports domain. And the output are summaries describing what happened in the game (e.g., who won/lost, ..., scored, etc.). We first describe our work on integrating fine-grained or micro plans with data-to-text generation. As part of this, we generate a micro plan highlighting which records should be mentioned and in which order, and then generate the document while taking the micro plan into account. We then show how data-to-text generation can benefit from higher level latent entity planning. Here, we make use of entity-specific representations which are dynam ically updated. The text is generated conditioned on entity representations and the records corresponding to the entities by using hierarchical attention at each time step. We then combine planning with the high level organization of entities, events, and their interactions. Such coarse-grained macro plans are learnt from data and given as input to the generator. Finally, we present work on making macro plans latent while incrementally generating a document paragraph by paragraph. We infer latent plans sequentially with a structured variational model while interleaving the steps of planning and generation. Text is generated by conditioning on previous variational decisions and previously generated text. Overall our results show that planning makes data-to-text generation more interpretable, improves the factuality and coherence of the generated documents and re duces redundancy in the output document
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