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Investigating factors that affect student engagement and academic performance in novice students in CS education
No full textAbstract not currently available
The impact of Helicobacter hepaticus infection on host immunity
Get PDFThe mammalian immune system has evolved alongside a complex microbiota. Microbial colonization drives constant immune responses at steady state, while microbiota-derived metabolites and signals have functional impacts on host immune cells. Helicobacter hepaticus (Hh) is a member of the murine intestinal microbiota with the capacity to drive immune responses in a context-dependent manner. Hh stimulates strong immune regulation which counterbalances the induction of effector responses and allows persistent colonization without pathology. Whether these interactions alter how the host immune system responds in a subsequent disease setting has not previously been explored. In this thesis, we aimed to investigate how Hh affects the outcome of inflammatory disease and test whether Hh drives phenotypic and functional changes to intestinal immune cells at steady state.
Here, we demonstrate that Hh colonization attenuates intestinal disease severity in the DSS colitis model. This was dependent on extended colonization with Hh prior to colitis onset and was not present immediately following infection, suggesting a mechanism by which Hh primes intestinal immune responses at steady state to alter disease outcomes. We found that Hh colonization stimulated increased monocyte and neutrophil infiltration to the colon at steady state and drove increases to local proinflammatory cytokine transcription. However, colonic macrophages from infected mice showed suppressed cytokine responses ex vivo, indicating that Hh functionally modulates local immune cells to limit inflammatory responses. We tested whether the disease attenuating effect was dependent on recognition of Hh by TLR2, with the aim of elucidating the mechanism through which Hh affects disease outcomes. We demonstrate that disease attenuation does not require TLR2 signalling, suggesting that a different mechanism drives disease protection in Hh colonized animals.
This work provides insight into how host immune functions are shaped by the resident immunomodulatory microbiota. As the role of the microbiota in health and disease is becoming increasingly apparent, it is critical to develop a greater understanding of these interactions. Our work supports the conclusion that the microbiota primes the intestinal immune system at steady state, thereby altering immune responses during inflammatory settings
Exploring Louis Cha’s martial arts novels in the English-speaking world: translation, dissemination and reception
Get PDFLouis Cha (1924-2018) is a representative writer of martial arts novels in contemporary Chinese literature, whose works have gained great popularity among the readers in Chinese communities. Cha’s works have been translated into English in the past few decades.
This thesis aims to explore how Cha’s works are translated, disseminated and received in the English-speaking world. Drawing on paratext theory, polysystem theory and reception theory that jointly serve as its theoretical framework, this thesis focuses on four English translations: (1) Fox Volant of the Snowy Mountain (1993), Olivia Mok’s translation of Xueshan Feihu, (2) the three-volume The Deer and The Cauldron (1997, 1999 and 2002), John Minford’s translation of Lu Ding Ji, (3) The Book and The Sword (2004), Graham Earnshaw’s translation of Shujian Enchou Lu and (4) Legends of the Condor Heroes (2018, 2019, 2020, 2021), Anna Holmwood, Gigi Chang and Shelly Bryant’s co-translation of Shediao Yingxiong Zhuan. To achieve the aims of the research, each case study first examines the translator and the translation strategy which affects the shaping of the translation, then it analyses the paratexts to illustrate how they play a role in enabling the translation to enter the target literary system and promote its dissemination. In order to grasp the reception of the translation and identify the affecting factors, each study devotes its last section to investigating two types of book reviews: literary reviews that are written by scholarly readers and published in journals or newspapers and popular reviews that are written by general readers and posted on the shopping website Amazon, the reading community Goodreads and the social media X.
This study finds that different translation strategies are employed to translate Cha’s works and they have affected the reception. It is recommended that collaborative translation be adopted to translate Cha’s lengthy novels. An analysis of the paratexts of the translations reveals a range of actors at work, thus accentuating an agent-driven and process-oriented approach. Studying the reviews illustrates that Legends of the Condor Heroes gained the best reception while Fox Volant of the Snowy Mountain ranked last. Moreover, studying the reviews identifies both the extratextual and textual factors that affect the reception. Adopting theories and approaches in Literary Studies and Translation Studies, this thesis highlights the importance of interdisciplinary studies and contributes to current studies by extending the research scope. It further points out the future directions in this field where multimodal translations of Cha’s novels should be taken into consideration
Analysis of the structure and function of CLIC4 in aqueous and membrane environments
No full textCLIC4 is a member of the CLIC family of soluble proteins that are capable of spontaneous incorporation into lipid intracellular membranes to form chloride selective ion channels. Given the critical functions of the biological plasma membranes, artificial lipid-based membranes mimicking the natural membranes have been used in characterizing membrane proteins in a native-like environment. Here in this study, His-tagged CLIC4 protein expression was optimized by testing in vivo and in vitro expression systems. Furthermore, the conformational structure of CLIC4 protein was examined in aqueous and in an artificial liposome membrane environment in presence and absence of oxidizing agent. Where, under non-reducing aqueous environment, CLIC4 tends to oligomerize upon incubation at 37oC in a time-dependent manner compared to the stable CLIC4 monomers at 4oC. In artificial liposome membrane environment, CLIC4 oligomerization appeared to be independent of the oxidizing environment. Given that, cysteine (Cys) residues in other CLIC family members have been implicated in the protein conformational structure, we attempted to investigate the impact of CLIC4 Cys residues on the CLIC4 conformational structure within the membrane liposomes. Indeed, PEGylation analysis of CLIC4 mutants, where Cys 35, Cys 100, Cys 189 and Cys 234 were substituted with serine indicates enhanced solvent accessibility at C35S and C189S compared C100S or C234S CLIC4 mutants, thus highlighting the impact of Cys 35 and Cys 189 on CLIC4 PEGylation. Furthermore, analysis of truncated CLIC4 protein fragments including 100, 150, 220 and 270 amino acids suggest that Cys 35 limits the solvent accessibility to CLIC4 protein compared to Cys 100, Cys 189 and Cys 234. However, the solvent accessibility to Cys 100 and Cys 189 were not impacted by Cys 35. Interestingly, in presence of Cys 35, Cys 234 appeared to negatively impact the solvent accessibility to Cys 100 and Cys 189. Taken together, these results highlight the critical role of Cys residues on the CLIC4 protein conformational structure and incorporation into membranes and further suggest that Cys 35 and Cys 234 could be target sites for further CLIC4 modification to induce targeted conformational changes
Estimating the glacial valley fill of the north-west Greater Caucasus Mountains using artificial neural networks
Get PDFGlaciation and subsequent glacier retreat has resulted in unknown quantities of sediments being stored in valleys throughout the Greater Caucasus Mountains. It is difficult to estimate the quantity of this sediment fill as a result of there being no direct measurements of the thickness of these sediments. In this study, valley cross-sections are extracted from a catchment area in the western Caucasus using a DEM. Training data comprised of valley widths and sediment depth estimates is obtained from these cross-sections based on assumptions about the geometry of glacially eroded valleys. This training data is used to train an artificial neural network to create a model which can be used to estimate sediment depths and associated volumes in other valleys in the Caucasus. This model was then applied to other valleys that were found to show evidence of glacial sediment fill. A volume of 42.05 ± 1.01 km3 is found from a combination of 7 valleys in the north-western and central part of the Caucasus which corresponds to a total mass of 8.83x1013 ± 8.67x1012 kg. The individual results from each valley showed that there is a relationship between the average width of the valleys and the maximum depth of sediment found within them. The results also highlighted that there are parts of the valleys that do not show evidence of glacial fill where they may be expected to. This presents implications for the glacial processes that impact the location of this sediment fill such as glacier motion and glacial erosion. The quantity and distribution of these sediments also have implications for isostatic adjustment associated with glacial retreat in the Caucasus as they demonstrate how mass has been transferred away from the mountains, which can contribute to the surface uplift resulting from ice mass loss
Optical screening and acoustic sorting of microfluidic droplets
No full textAbstract not currently available
Characterising respiratory viral infections and cross-reactive immunity among hospitalised and community cohorts during and post-COVID-19 pandemic
Get PDFAcute respiratory tract infections carry a high burden of morbidity and mortality across the world. A significant proportion of these infections are caused by respiratory viruses, however the aetiology and epidemiology of respiratory viral infections are poorly characterised. The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) in 2019 and the subsequent COVID-19 (Coronavirus disease 2019) pandemic, has further changed the landscape of viral respiratory tract infections and highlighted the importance of understanding the contribution of respiratory viruses to respiratory infections.
Methods:
Multiplex respiratory PCR (polymerase chain reaction) was performed on upper respiratory tract (URT) samples from 1002 hospitalised SARS-CoV-2 positive patients recruited to the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) study between February 2020 and June 2021 in the UK to investigate the prevalence and impact of viral co-infection on disease severity.
Within a prospective longitudinal cohort of randomly selected households, in an urban and rural site in Malawi, adult participants provided URT samples at four timepoints between February 2021 – April 2022. Comprehensive clinical, exposure risk, and socio-economic data were combined with results of multiplex respiratory PCR to investigate endemic respiratory virus circulation patterns in a country that implemented less restrictive non-pharmaceutical interventions (NPIs) than the UK.
An enhanced surveillance study of severe acute respiratory infection (SARI) patients admitted to a large hospital in Glasgow, UK, was carried out between January 2023 and March 2024. Clinical and routine NHS data was collected for 780 participants, and URT samples were tested by PCR for a wide range of respiratory viruses, to investigate the epidemiology of SARI in the post-pandemic era.
Phage immunoprecipitation and sequencing (PhIPSeq) technology was used to screen serum samples from 160 SARS-CoV-2 vaccinated or infected participants, plus pre-pandemic controls, for epitope level immune responses to SARS-CoV-2, and potential cross-reactive responses to other human and animal coronaviruses.
Results:
Viral co-infections in hospitalised UK COVID-19 patients in the early waves of the pandemic were rare. In Malawi, during the pandemic, respiratory viruses continued to circulate in the community with SARS-CoV-2 and rhinovirus detected most frequently. Influenza, RSV (respiratory syncytial virus), and viral co-infections were rarely detected. Distinct differences in respiratory virus epidemiology and population demographics were seen between the rural and urban sites.
In our post-pandemic enhanced surveillance study in a single busy UK centre, almost half of SARI cases tested positive for a respiratory virus; SARS-CoV-2, rhinovirus, and influenza viruses were most frequently detected. Routine testing would have missed over half of these diagnoses. A diagnosis of viral SARI, particularly made at the hospital front door, was associated with significantly lower antibiotic prescribing rates and a shorter hospital admission, compared to those that tested respiratory virus-negative. Viral co-infection prevalence was low and detected in younger, less comorbid/frail participants. In-hospital mortality was 2.5%. Charlson Comorbidity Index (CCI) score ≥ 5, respiratory rate >20 breaths per minute at admission, and an oxygen requirement at admission were all independent predictors of death whilst SARS-Cov-2/influenza virus mono-infection and chronic lung disease were predictive of survival.
PhIPSeq analysis of serum samples detected higher magnitude immune responses to spike epitopes following vaccination with mRNA vaccines compared to the AstraZeneca vaccine or SARS-CoV-2 infection. Immunoreactivity differed by individual epitopes; strong antibody responses targeting the spike fusion peptide were restricted to SARS-CoV-2-convalescent individuals. Evidence of cross-reactive responses directed against human coronavirus (HCoV) OC43, SARS-CoV, and bat/pangolin coronaviruses was demonstrated.
Conclusion:
Respiratory virus epidemiology has evolved over the course of the COVID-19 pandemic across the world and will continue to change in the future. Ongoing enhanced surveillance to map this evolution, and to detect emerging pathogens, is essential for healthcare planning and pandemic preparedness. New technologies such as PhIPSeq have potential to aid in high throughput pathogen screening, epitope level immune response analysis, and vaccine design
Formal verification of safety-critical systems with uncertainty for Industry 4.0 applications
Get PDFIndustry 4.0 adopts Internet of Things (IoT) and service-oriented architectures to integrate Cyber-Physical Systems (CPSs) and Enterprise Planning systems into manufacturing operations. Furthermore, manufacturing processes typically involve the composition of various modular CPSs that work as a whole, such as multiple Collaborative Robots (cobots) working together as a production line, improving the production process’s flexibility and resilience. On the other hand, it is still challenging to verify this kind of compositional process and take into account uncertainties from IoT sensors and decision-making algorithms. For example, the trustworthiness of the sensors is essential to guarantee performance, safety and product quality during operation. However, existing methodologies to test such systems often do not scale to today’s sensor networks’ complexity and dynamic nature.
Formal model verification techniques are a valuable tool that allows strong reasoning about the high-level design of CPSs. However, the uncertainty exhibited by the underlying sensor networks is often ignored. Moreover, existing model-checking tools are hard to adapt to the dynamic environment of Industry 4.0 applications during the operation stage, such as an Automated Guided Vehicle (AGV) joining in accompanying the manufacturing process at run time.
This thesis proposes a novel run-time formal verification framework for modular CPSs that combines sensor-level data-driven fault detection and system-level probabilistic model checking. The resulting framework can quantify sensor readings’ trustworthiness, enabling formal reasoning for system operation behaviour and reliability analysis.
The proposed approach is evaluated on three use cases, including an industrial turn-mill machine equipped with a sensor network to monitor its main components continuously, a passenger lift with two sensor networks to monitor the door and cabinet car movements, and a two-cobot painting process running with Robotic Operation System (ROS). The results indicate that the proposed verification framework involving the quantified sensor’s trustworthiness enhances the accuracy of the system failure prediction and potentially optimises manufacturing processes
Examination of vascular smooth muscle cell-specific NADPH oxidase 5 in the context of age, sex, and angiotensin II-induced hypertension: implications for cerebrovascular disease
Get PDFSummary available: pages iii-vi
Toward manipulating user perceptions of objects by altering interaction sounds
Get PDFHumans naturally use interaction sounds emitted from physical contact with objects to gather information about their properties, such as size, texture, and quality. Augmenting these interaction sounds may manipulate our perception of the object’s properties. Furthermore, such augmentation could be useful in conveying extra information. For instance, augmenting the perceived weight of a cup by manipulating the interaction sound could help users track their daily food and carbohydrate intake to aid them in their diet. While previous work has demonstrated the effect of reverb on room size perception in various contexts, such as VR gaming, few studies have explored the potential of manipulating interaction sound, such as adding reverb or changing the sound, to alter user perception of object properties.
In two experiments, this thesis explored the effects of different auditory feedback (surface materials, musical instruments) and reverb parameters (mixing, depth) on perceived simultaneity, unity, agency, and object properties (object size, material, and room size), along with their recognition. Through the experiments, it was discovered that modifying the sounds emitted from tapping an audible object can affect our perception of its size and the size of the room in which it is located. In regards to the user ability to recognize auditory feedback , it was discovered that auditory feedback did not considerably impact the accuracy of audio recognition, whereas reverb played a more significant role.
This thesis presents a discussion of the findings, along with the limitations of the current study and suggestions for future research. Lastly, it provides guidelines on augmenting interaction sounds based on our experiments and findings
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