Search

This three-paper dissertation systematically investigates the methodology issues related to using observational systems to observe, analyze, and interpret teachers' reformed teaching practices within the K-12 classroom context. Each paper contributes a distinct perspective to evaluate instructional practices accurately, consistently, and effectively in science classrooms. The first paper offers a systematic literature review on classroom observation protocols (OPs) used for evaluating science teaching practices. In this study, I proposed an analytical framework, underpinning four crucial aspects of OP studies: the research objectives, design, data collection strategies, and data analysis and interpretation. This framework serves as the cornerstone for analyzing 37 distinct studies that have used OPs to evaluate the instructional practices of K-12 science teachers. The study underscores the need for transparent rater training procedure, sampling choices, and the advanced statistical techniques to address rater-associated variances and eventually enhance the reliability and validity of the teacher measures. The study also suggests continued development of OPs that are aligned with current and future science education standards and the application of advanced statistical methods to examine rater effects in classroom observation studies. In the second paper, we developed a comprehensive classroom observational system, utilizing the Rasch model to validate the instrument, guide rater training, and analyze observational data. We implemented this system with 321 full-length high school chemistry classroom observation videos. We proposed this system, because the exclusive reliance on developing new OPs may not lead to valid and reliable measurements of instructional practices, as ratings are often affected by construct-irrelevant variances such as rater bias and data analysis strategies. This study shifts the focus from the OPs alone to a classroom observation system that includes instrument validation, rating training, and data analytical strategies. The psychometric evidence in this study supported this system's feasibility of yielding reliable measures of instructional practices. The third paper examines rater effects by applying a Partial Credit Many-Facet Rasch Measurement (PC-MFRM) in a science classroom observation context. As shown in the first two papers, classroom observation studies employing OPs are mediated by human raters, who are susceptible to errors. These errors introduce construct-irrelevant variance, which can adversely impact the validity and reliability of measurement of instructional practices. This study aims to identify and control these variances, particularly focusing on three rater effects: rater severity, central tendency, and the halo effect. I applied PC-MFRM to concurrently examine the three rater effects and their impacts on measurement of instructional practices. MFRM results indicate the significant discrepancies in rater severity and identified the specific raters who showed central tendency and halo effects. The finding suggests that researchers can incorporate MFRM diagnostic information throughout the rating training and calibration process to reduce any potential halo and central tendency. To address the rater severity, researchers should focus on intra-rater consistency as well rather than inter-rater reliability only. This study extended the application of MFRM to classroom observation by offering a multi-dimensional understanding of rater effects; thereby it contributed to the improvement of rater training process, which can consequently enhance the reliability and validity in measuring teaching practice. The validity and reliability of classroom observations for evaluating teacher practices hinge considerably on rater effects and the systematic evaluation the impact of rater-related effects. While Observation Protocols (OPs) provide a structured framework for such evaluations, the literature indicates that rater behavior introduces construct-irrelevant variances such as rater severity, halo effect, and central tendency. Previous studies have employed the Many-Facet Rasch Model (MFRM) to examine some of the effects, but these efforts have predominantly focused on single-dimensional analyses. Addressing this research gap, current study applies MFRM to concurrently investigate three critical rater effects--rater severity, central tendency, and halo effect--in the context of a longitudinal efficacy study on the Connected Chemistry Curriculum (CCC). Specifically, we aim to (1) assess the degree to which MFRM can identify the presence of these rater effects, and (2) evaluate the implications of using MFRM on enhancing rater training programs for classroom observations. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The capacity of educators to dynamically adjust their thought processes and behaviors in response to the diverse needs and characteristics of students in an unfolding teaching situation is widely acknowledged as a cornerstone of effective teaching. While teachers' instructional adaptations have been documented and studied from various angles, the field lacks a robust theoretical framework that precisely distinguishes yet cohesively integrates teachers' cognitive processes and capabilities of adaptive teaching. Addressing this gap, this dissertation presents the Teacher Adaptive-Cognition Theory (TACT), an innovative theoretical framework that aims at providing a comprehensive and much-needed perspective on the cognitive complexity inherent in adaptive teaching. Formulated through a critical and extensive review of adaptive cognition within and beyond the field of teaching, the TACT model distinguishes among behavioral performance of adaptation, cognitive performance of adaptation, and cognitive readiness for adaptation. It posits that analyses of the cognitive processes and capabilities of adaptive teaching should be systematically contextualized within each other. Furthermore, the dissertation delves into the implications of the TACT model for both research and practical application within and beyond the realm of teacher adaptability. By providing this detailed, integrative framework, this dissertation aims to enhance the conceptual clarity needed to guide research in the study of the crucial skill of teacher adaptability in particular and adaptive expertise in general, as well as to foster the development of such skill. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Excessive scarring (keloids and hypertrophic scars) is complex with incompletely understood genetic underpinnings. The manifestation of a severe excessive scarring phenotype in an Israeli pedigree carrying a very rare homozygous frameshift variant (p.Asn43fs/rs571313759) in the C1QTNF12 gene, encoding adipolin, provided an opportunity to study its potential role as a highly penetrant causal variant. Both in vitro and bioinformatics approaches were adopted, with the latter extended to examine risk patterns of excessive scarring in a wider population. To characterise the phenotype of dermal fibroblasts carrying the variant, cells isolated from the proband were analysed for their morphology, proliferation, and contractility. These cells had enhanced transforming growth factor beta 1 (TGFβ1)-induced contractility but no differences in morphology or proliferation. To assess the effect of adipolin on fibroblast contractility, wild-type normal human dermal fibroblasts were treated with recombinant adipolin and contraction assays performed. No effect on intrinsic or TGFβ1-induced contractility was demonstrated. To generate insight into the effect of adipolin on the fibroblast transcriptome, normal human dermal fibroblasts were treated with adipolin-conditioned media and bulk RNA-sequencing was performed. No significant transcriptomic changeswere induced, suggesting that adipolin may not have a striking direct effect on dermal fibroblasts. To further substantiate the evidence for or against C1QTNF12 loss-of-function (LOF) in fibrosis, exome data for ~200000 participants in the UK Biobank (UKB) was interrogated for potentially relevant phenotypic traits. No phenotypes of clinical relevance to excessive scarring were observed in individuals with C1QTNF12 LOF variants. Multivariable logistic regressions and a phenome-wide association study (Phe-WAS) was performed within the UKB excessive scarring cohort to characterise comorbid associations with excessive scarring. Previously reported associations withhypertension, vitamin D deficiency and atopic eczema were identified in models adjusting for age, sex and ethnicity, but only the association with atopic eczema (OR 1.68, p<0.001) was statistically significant after accounting for additional potential confounders. Ethnic differences in these comorbid associations were highlighted. The PheWAS identified numerous previously unreported disease associations that may inform on common pathological mechanisms, including musculoskeletal disease and pain symptoms. To investigate for common genetic variations that associated with excessive scarring, a genome-wide association study (GWAS) was performed for the UKB cohort and meta-analysed with GWAS summary statistics from FinnGen, comprising anindependent European population. Three of four previously associated loci were identified: two at genome-wide significance (1q32.1: rs35383942, odds ratio [OR] 1.46, p-value 7.0×10-11; 1q41: rs10863683, OR 0.69, p-value 3.0×10-25) and one just short thereof (15q21.3: rs60890210, OR 1.24, p-value 6.7×10-8). Bayesian finemapping offered strong evidence for causality of the lead SNP at 1q32.1 (posterior probability [PP] 0.79) and 1q41 (PP 1.0) but was inconclusive at 15q21.3. Expression quantitative trait loci (eQTL) were identified for ten genes including PHLDA3 and NEDD4 but colocalisation analysis did not support the hypothesis that these eQTLs shared a causal variant with keloid susceptibility. A known association with Dupuytren's contracture was identified at the 15q21.3 locus, notable as a fibrotic disorder, hinting at a shared genetic architecture. Data from this work suggest that the C1QTNF12 variant may not be a highly penetrant cause of excessive scarring in our pedigree but does not fully rule out a contributory role to the development of this complex disease. The UKB analyseswere a broad examination of the phenotypic and genetic characteristics of excessive scars, with findings that parallel previous reports and shed light on new associations. Importantly, they highlighted the need for better representation of skin phenotypes in electronic health records for future research.

Inherited pathogenic variants of surfactant protein C (SFTPC) can cause familial pulmonary fibrosis. The most common, SFTPC-I73T, aberrantly localises to the plasma membrane and causes alveolar type 2 (AT2) dysfunction via a poorly understood toxic gain-of-function. Understanding the mechanisms of SFTPC trafficking and their interactors in health and disease is crucial to defining how pathogenic variants induce cellular dysfunction. To investigate trafficking components required for SFTPC trafficking that are perturbed by the I73T variant, I undertook SFTPC-WT and -I73T proximity labelling using TurboID and identified labelled proteins by mass spectrometry. I discovered >100 proteins preferentially labelled by SFTPC-WT and therefore likely to be required for normal SFTPC trafficking. I undertook validation of biologically relevant hits by CRISPR/Cas9 deletion of candidates involved in membrane trafficking, ubiquitination and lysosomal acidification. I found that many induced misprocessing and relocalisation of SFTPC-WT to the plasma membrane, phenocopying the I73T mutation. I undertook further validation of top hits in a novel CRISPR interference AT2 organoid model. I also undertook an exploration of the biology of MPZL1, a poorly characterised Ig-superfamily member which differentially interacts with, and is relocalised by, SFTPC-WT and I73T. This suggests that the normal function of MPZL1 may require interaction with SFTPC-WT. I defined novel aspects of its expression, cleavage and activation and showed from RNA sequencing that MPZL1 activation upregulates genes involved in cell migration; this may be crucial for AT2 function in alveolar repair. Together, this work has identified novel interactors involved in SFTPC trafficking and explored the biology of MPZL1, offering further insights into how SFTPC-I73T contributes to the development of pulmonary fibrosis.

Microalgae is known to produce numerous bioactive compounds for instance proteins, fatty acid, polysaccharides, enzymes, sterols, and antioxidants. Due to their valuable biochemical composition, microalgae are regarded as a very intriguing source to produce novel food products and can be utilised to improve the nutritional content of traditional foods. Additionally, microalgae are used as animal feed and additives in the cosmetics, pharmaceutical as well as nutraceutical industries. As compared to other terrestrial plants and other microorganisms, microalgae possess few advantages: (1) rapid growth rate; (2) able to grow in non-arable land and harsh cultivation conditions; (3) low nutritional requirements; (4) high productivity; and (5) reduce emission of carbon dioxide. Despite the large number of microalgae species found in nature, only a few species are identified and commercialized such as Chlorella sp., Spirulina sp. Haematococcus pluvialis, Nannochloropsis sp. and Chlamydomonas reinhardtii, which is one of the major obstacles preventing the full utilisation of microalgae-based technology. This thesis provides information on the overall composition of mixed microalgae species, Desmodesmus sp. and Scenedesmus sp., for instance protein, carbohydrate, lipid, antioxidants, and pigment. This thesis firstly introduces the application of triphasic partitioning (TPP) in the extraction and partitioning of the biomolecules from the microalgae. The latest advancement of technology has evolved from a liquid biphasic flotation (LBF) to TPP. T-butanol and ammonium sulphate are used in TPP to precipitate desired biomolecules from the aqueous solutions with the formation of three layer. TPP is a simple, time- and cost- efficient, as well as scalable process that does not require toxic organic solvents. Lipase is abundantly produced by microbes, bacteria, fungi, yeast, mammals, and plants. Lipase is widely used in the oleochemical, detergent, dairy, leather, cosmetics, paper, cosmetics, and nutraceutical industries. Therefore, this thesis also discusses the possibility of identifying and extracting enzyme lipase from the microalgae using LBF. Several parameters (volume and concentration of solvents, weight of biomass, flotation kinetics and solvent types, etc.) have been investigated to optimize the lipase extraction from LBF. Chlorophyll is the main pigment present in the microalgae. Thus, this work proposes the digital imaging approach to determine the chlorophyll concentration in the microalgae rapidly because the chlorophyll content has a significant impact on microalgae physiological health status as well as identifies the chlorophyll concentration in the production of by-products. Lastly, microalgae oil can be used as the feedstock for biodiesel as well as nutraceutical, pharmaceutical, and health-care products. The challenge in the lipid extraction is the co-extraction of chlorophyll into the oil, which can have serious consequences for downstream processing. Therefore, the removal of the chlorophyll from the microalgae using activated clay or sodium chlorite in the pre-treatment procedure are examined. The research achievements in these works and future opportunities are highlighted in the last chapter of the thesis.

This thesis aims to address the issue of anatomical changes during the treatment of head and neck cancer patients. Intensity-modulated proton therapy (IMPT) shows advantages in delivering a conformal dose to the target while minimizing the dose to the adjacent normal tissue. However, in the delivery of IMPT, patients not being static can lead to dosimetric discrepancies. This thesis explores different techniques to reduce the influence of uncertainty from anatomical changes (anatomical uncertainty). In Chapter 3, anatomical variations are incorporated to reveal the robustness of a plan, thus improving the selection of a robust plan. The benefit is demonstrated in all beam arrangements used in the study. In Chapter 4, a probability model is developed to simulate major anatomical deformations at each weekly time point based on population data. For overall anatomical uncertainty prediction during treatment, the PM reduces anatomical uncertainty from 3.72±0.46 mm (no model) to 0.81±0.56 mm on average. In Chapter 5, an individual model is developed to refine the systematic prediction of population data using individual progressive information. Compared with no model, whose average anatomical uncertainty and gamma index are 4.47±1.23 mm and 93.87±0.83% at week 6, respectively, the refined individual model reduces anatomical uncertainty to 1.89±1.23 mm and improves the gamma index to 96.16±1.84% at week 6. In Chapter 6, a proposed flexible strategy creates upfront predicted replans on the predicted individual geometries from the RIM. This application of the RIM reduces the parotid Dmean by 0.53 Gy on average, achieving the minimum benefit of non-delay treatment, while the dosimetric of other organs has no significant difference with the standard replanning technique (p > 0.05). This prediction-based replanning improves clinical workflow efficiency. This research integrates computational methods into IMPT treatment for head and neck patients. New perspectives for mitigating anatomical uncertainty are provided and discussed in this thesis.

Photonic technologies have been considered new methods to achieve high bandwidth data communication and transmission. Si-photonics was proposed to address the discrepancy between bulky photonic devices and advanced electronics and create high-density integrated photonics. One of the challenges is integrating all the components necessary for full-functionality photonic integrated circuits (PIC). Great efforts have been devoted to overcoming the inherent limitations of Group-IV materials to provide sufficient gain, efficient modulation and sensitive detections. Making Si the host material for efficient light emission poses the most stringent requirements and is the primary missing component in the Si-photonics platform. Incorporating III-V materials with the Si photonics platform and quantum dot (QD) structure is a promising solution to the problem of a fully-integrated and high-functioning PIC. High-performance QD lasers on III-V substrate or epitaxially on silicon have been developed in the last few decades with low threshold current density, low-temperature sensitivity, great reliability and large injection efficiency. Moreover, from the dynamic aspect, the intrinsic frequency of direct modulated laser and noise intensity is important for its applications in a data centre. QD is considered an alternative to quantum wells (QWs); however, the demonstrated QD laser has not fulfilled initial expectations, mainly due to its high gain compression and low differential gain. Another feature that needs to be noticed is feedback sensitivity, as the properties of semiconductor lasers are greatly degraded by reflection from external reflectors, such as the fibre connects and facets of integrated devices. QD devices are predicted to have stronger feedback resistance due to their large damping and small linewidth enhancement factor (LEF). These properties have attracted much research, and high-performance QD devices have been developed. In this thesis, we comprehensively investigated QD laser performance and applied our QD laser in the optical module instead of the commercial QW distributed feedback (DFB) laser. The background of Si photonics, the development of QD devices, and the fundamentals of QD lasers are presented in Chapter 1. The basic static and dynamic performances are demonstrated in Chapters 2 and 3. The GaAs-based QD laser provides a low threshold, high-temperature stability, and low noise operation with a limited small signal bandwidth. Chapter 4 provides a comprehensive study of the feedback resistance of the QD laser. The onset of coherence collapse is determined as -14 dB, verified by the static optical and electrical spectra and small signal response. Based on previous measurements, the QD laser is proven to be a high-performance, low-cost candidate for the Si-photonics module. In Chapter 5, the QD laser is used in practical applications, including a large signal transmission system with and without feedback and a commercial optical module. Although the intrinsic bandwidth of the QD laser is limited to around 5GHz due to the large damping and unoptimised capacitance, 30 Gbps data transmission has been demonstrated by a directly modulated QD laser. Large, high-speed signal modulation is achieved due to its high gain compression factor. Regarding the laser with intentional feedback, there is little degradation in the eye diagram under the whole feedback level up to -8dB. We also replaced the commercial QW DFB laser in 100G data-centre reach (DR)-1 optical module with our QD Fabry Perot (FP) laser without an isolator which gives a clear eye diagram under 53 Gbps 4-level pulse amplitude modulation (PAM4) with an extinction ratio (ER) of 4.7 dB. In conclusion, this thesis verifies the feasibility of adopting the QD laser as a light source for the Si-photonics module. The QD laser is selected over other lasers because of its low threshold, high-temperature stability and maximum operating temperature, and strong tolerance to unintentional feedback. This is the first project to measure critical feedback levels with different characteristics and to theoretically analyse the inconsistent value. More importantly, this thesis' most original contribution is investigating the commercial applications of QD lasers in a Si-photonics module in an isolator-free state. In summary, the QD laser has been proven to be a feasible solution for the next-generation optical system.

Glioblastoma multiforme (GBM) is the most malignant adult brain tumour. A subpopulation of cells, termed glioblastoma stem cells (GSCs), possesses similar phenotypic characteristics to normal neural stem cells (NSCs) and may drive tumorigenesis. GSCs frequently express many essential neurodevelopmental transcription factors (TFs) at high levels. Of particular note are SOX2 and SOX9 genes, which are master regulatory TFs in the forebrain development with reprogramming activity that are essential for GSC self-renewal. Here we explored a set of newly identified small-molecule compounds that was shortlisted following phenotypic screening for loss of SOX2 in GSCs. We showed that a subset of these hits operates via the ubiquitin-proteasome system (UPS), revealing a potentially new pathway controlling SOX2 and SOX9 protein turnover. We demonstrated that these compounds likely act through a class of enzymes called deubiquitylases (DUBs). The lead compound 1035 was validated across a range of different patient models using two orthogonal reporter lines. We also confirmed that the endogenous protein was degraded via a proteasomal mediated pathway. We explored the selectivity of effects on cell viability and proliferation using an independent panel of non-GBM cell lines, including human umbilical vein endothelial cells, fibroblasts, non-tumour pericyte-like cells as well as human pluripotent stem cells (hPSCs)-derived neuroepithelial. The compound appeared selective, yet had some degree of off-target toxicities at higher doses. However, we did notice a strikingly significant positive correlation between the effect on GSC proliferation and SOX2/SOX9 expression levels. USP36, USP39 and USP42 were determined as potential DUB targets to which 1035 might bind, based on their restricted subcellular localisation to the nuclear/nucleolar compartments, in addition to lower SOX2/SOX9 abundance after individual knockdown. Concurrent deletion of these USPs was also able to phenocopy the compound effects, with diminished cell viability as well as proliferative arrest, alongside a robust SOX2 and SOX9 protein decline. Next, four structural analogues of 1035 were significantly less effective in overall at reducing endogenous SOX2 and SOX9, implying that the presence of a chiral carbon atom or/and methyl group at the asymmetrical carbon position is/are absolutely critical to retain compound activity. Individually purified R or S enantiomer was unexpectedly less potent than the original 1035, but this was restored in a racemic mixture, consistent with both enantiomers possibly operating together with a concerted synergism. The right-handed stereoisomer R mainly facilitated SOX2 and SOX9 protein degradation via USP42 (and maybe USP36 to a limited extent); meanwhile the left-handed stereoisomer S gave rise to broad cytotoxicity via nucleolar disruption pathway in a non-cell-selective manner. The structure-activity relationship can then be applied for future medicinal chemistry optimisation to improve lead compound potency and on-target specificity, whilst minimising the non-selective killing impact on normal human cells.

We are interested in the efficient numerical solution of the structured linear systems that arise when we apply stochastic Galerkin mixed finite element methods (SGMFEMs) to systems of partial differential equations (PDEs) with inputs that depend on a possibly large number of uncertain parameters. In particular, we are interested in PDEs arising in engineering applications for which SGMFEMs give rise to saddle point systems, such as linear elasticity and fluid flow problems. Despite being highly structured, saddle point systems associated with SGMFEMs are challenging to solve due to their extremely large size. The number of equations is the product of (i) the number of degrees of freedom associated with the chosen mixed finite element method on the spatial domain and (ii) the dimension of the polynomial space associated with the parameter domain. When we refine the finite element mesh and/or increase the degree of the parametric polynomial approximation to improve accuracy, the dimension of the associated linear system increases. When working on standard desktop computers, one cannot use conventional Krylov subspace methods for very fine SGMFEM discretisations because storing the required matrices and vectors quickly exhausts available memory. One potential remedy is to recast the discrete problem as a linear multi-term matrix equation (LMTME) and use reduced basis methods. Such methods construct low rank factored approximations to the solution matrix by projecting the problem onto a lower-dimensional space. Our main aim is to develop a memory efficient solver for the discrete problems that arise when we apply SGMFEMs to a three-field linear elasticity model with parameter-dependent Young modulus. The starting point is a reduced basis method known as Multi-RB that was recently proposed for LMTMEs associated with symmetric and positive definite problems. After reformulating the matrix equation, the scheme iteratively constructs a reduced basis using a strategy inspired by rational Krylov subspace approximation, then applies Galerkin projection and solves a reduced problem. When the problem is not positive definite, the best choice of preconditioner and projection technique to apply is not clear. For large-scale problems with solutions that cannot be approximated well by very low rank matrices, selecting a computationally feasible stopping condition is also problematic. We modify the Multi-RB method to solve LMTMEs associated with symmetric and indefinite problems. For the linear elasticity problem of main interest, we critically assess the performance of the method using two distinct preconditioning strategies and two projection techniques. We also provide new eigenvalue analysis for the preconditioned systems. For smaller problems, we examine the convergence of the method by tracking the preconditioned and unpreconditioned residuals. Finally, to compare how the solver behaves on a different LMTME with the same structure, but whose solution matrix has different rank characteristics, we also consider a two-field groundwater flow model with parameter-dependent permeability coefficient.

Purpose and Method of Study: The purpose of this study is to delve into the bicultural heritage and educational experiences of East Asian American women, exploring their path to leadership roles. Using qualitative research methods, including semi-structured interviews, the investigation sheds light on the unique challenges and opportunities faced by East Asian American women leaders as they progress on their leadership journey. The focus of the study was to gain a deeper understanding of the perspectives and experiences of these women. Findings and Conclusions: The study employed a qualitative narrative approach (Creswell, 2013) to gather data, and three main themes emerged from the analysis: the path to leadership, challenges in achieving leadership in the profession, and the advantages and opportunities of the participants' international bicultural backgrounds. Participants described the importance of mentors, the necessity of breaking stereotypes, and international study as crucial factors in their careers. They discussed the challenges of communication barriers, invisibility, and lack of professional connections as well as the advantages and opportunities their international backgrounds provided, including their unique skills and perspectives. The lives and careers of these women serve as inspiration and encouragement for the next generation of Asian American women leaders. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The current study aimed to increase the efficacy of the implementation of a large-scale school-based mental health service model in a public school district in collaboration with a university-led community mental health coalition. Specifically, the study evaluated the effectiveness of a web-based social intervention targeted for teachers designed to enhance their role clarity and identification within school-based mental health practices. Youth mental health challenges are prominent and rising, with many schools adopting a MTSS model focused on prevention (Merikangas et al., 2010; Reinke et al., 2008). While a teacher's role in youth mental health has been consistently emphasized, (Flaherty et al., 1996; Reinke et al., 2011; Weist et al., 1999), their involvement, engagement, and attitude towards their role have been questioned (Ekornes, 2015; Weist et al., 2012). Applying Social Influence Theory Principles of Persuasion (i.e., reciprocation, social validation (norming), legitimate authority, liking, scarcity, and commitment/consistency), (Cialdini & Griskevicius, 2010) the present study aimed to provide a brief training to teachers to decrease their role confusion and increase their role identification as gatekeepers of mental health in schools to further the use of data-based decision making in universal screening and utilizing evidence-based behavioral interventions in the classroom. The study contributes to the field of school psychology by emphasizing the need of school-community partnership while increasing teacher understanding of mental health supports in schools, firmly establishing prevention efforts in systems-level capacity building to enhance intervention efforts. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The outbreak of the COVID-19 pandemic in 2020 caused unexpected and unprecedented disruptions worldwide, inflicting inconvenience in daily life, heightened health risk, and psychological distress. University students, especially international students, faced unique challenges and stressors related to education, financial situation, safety, mental health, future planning, as well as COVID-19-related anti-Asian xenophobia and discriminations and student visa regulations. This mixed-method secondary data analysis study aimed to investigate the experiences, stress, adjustment, and ways of coping of international students during the COVID-19 pandemic. The results showed that international students experienced different stressors and utilized different coping strategies compared to their domestic American counterparts. International students also reported changes in experiences during the COVID-19 pandemic, stressors, and coping strategies over the course of six months. Implications of the findings as well as limitations and future directions were discussed. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The purpose of this participatory action research project (PAR) was to study how a group of teachers designed and implemented strategies with the intent of amplifying joyful learning experiences for Chinese English Language Learners (ELLs). The research focused on four classroom teachers in an elementary school as Co-Practitioner Researchers (CPR) who worked collaboratively to articulate the characteristics of joyful learning, co-design an observation tool, and select and implement culturally and linguistically responsive joyful learning strategies for Chinese ELLs. The researchers incorporated Community Learning Exchange (CLE) processes, three PAR cycles of inquiry, and collaborative work. Using the axioms of CLE, we learned together by engaging in deeper understanding of the potential cultural and historical influences in Chinese ELL students' learning and through authentic experiences of examining our practices in classrooms. Through data analysis of evidence from observations, CPR member reflections, documents, and artifacts, two key findings emerged from the PAR study: (1) teachers who cultivate intentional relationships with students support a safe and joyful learning environment for students; and (2) teachers who plan and implement lessons with specific CLRP strategies support ELL equitable access, academic rigor, and agency. Based on the study findings about how teachers can collaborate to shift their practices to incorporate more access and rigor for ELL students, school leaders can consider three recommendations when designing professional learning and facilitating instructional shifts: foster a learning environment with gracious space to empower staff; cultivate relational trust and agency to engage collaborative work; and center learning on strengthening teachers' culturally and linguistically responsive practices to amplify students joyful learning experiences. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

One of the key objectives in neuroscience is to understand how the brain processes sensory information to generate perception and guide decisions. Sensory processing has been studied extensively, primarily from a hierarchical perspective with a focus on the processing along ascending pathways. However, ascending sensory pathways are accompanied by descending connections at various levels of processing, yet their contributions to sensory processing remain unclear. In this thesis, I studied one of the major descending circuits in the central auditory system, the cortico-collicular pathway, which connects the auditory cortex (AC) to the auditory midbrain (i.e. the inferior colliculus, IC). To understand the role of this pathway during sound-guided behaviour, I used two-photon calcium imaging to measure the activity of neurons in the IC that receive projections from the AC while manipulating the AC inputs during a sound detection task. I found that individual cortico-recipient inferior colliculus (CRIC) neurons exhibited heterogeneous patterns of activity, and that the AC appears to be involved in influencing some of these patterns. Further, I showed that the CRIC trial-by-trial network activity contained behaviourally-relevant information, and that this information was more unreliable when the AC input was removed. Overall, this work offers novel insights into the neural and behavioural function of the auditory cortico-collicular pathway, which contributes to our understanding of the role of descending sensory pathways in perception and behaviour.

This thesis examines the relationship between city-regional networks and the geography of innovation in the UK. Social and economic networks are vital to the economic vitality and creative dynamism of cities. They are the social infrastructure connecting individuals, ideas, and places--bringing them together in novel and more productive ways-and generating opportunities to advance the technological frontier. The complex patterns linking individuals and communities also affect performance by unevenly structuring access to economic opportunities. Network diversity at the city-regional scale likewise contributes to divergent local development by constraining prospects for cluster growth and technological upgrading. Social networks are broadly acknowledged as the locus of high-technology innovation. Unfortunately, insight into the causes and mechanisms underpinning the social gains of city-regional networks remains thin: networks with open structure are pervasively thought to underpin high-tech cluster success, yet this critical assumption has remained unexamined; the roles and contributions of networked individuals on regional innovation has yet to be systematically studied; and the question of how new high-tech industries at the cutting-edge emerge vis-à-vis networks in related industries has not received sustained examination. Moreover, the empirical literature has focused on a relatively limited set of prominent agglomerations-partly due to a lack of appropriate relational data to construct city-regional networks-leaving open questions of generalizability beyond these settings. This thesis makes five substantive contributions towards remedying these research gaps. First, it integrates emerging large-scale data sources and develops novel datasets to build and analyse UK city-regional networks. Second, it examines the impacts of highly connected individuals - 'dealmakers' - on local performance, finding a causal effect of regional dealmakers on innovativeness productivity. Third, it evaluates their asymmetric roles relative to other actors in importing externally sourced knowledge 4 into city-regions. Fourth, it systematically revisits foundational claims about the importance of open networks in sustaining highly innovative places. It develops a new measure of network openness by synthesizing complex multidisciplinary debates. It finds a causal effect of open networks on subsequent high-tech growth - the findings also suggest limits to open network effectiveness. Fifth, it provides a first empirical examination of emerging frontier industries focusing on fintech, exploring how much of its development has been shaped by antecedent capabilities and the social organization of regional finance and digital economy industries. The findings suggest that open network structures in the disrupting antecedent industry drive new industry growth.

Twentieth-century China witnessed devastating wars, radical political revolutions, and, recently, very rapid economic development that lifted hundreds of millions from dire poverty. The economic development profile of this century of revolutions has not been described with consistent and reliable data, leaving open debates on China's transition to modern economic development. My Ph.D. project identifies jiapu (Chinese lineage genealogies) as a novel, reliable, and consistent source which allows me to reconstruct the changing occupational structure of twentieth-century China. Jiapu record individual-level information of descent groups with a common ancestor together with biographies detailing the life course of some members. The value of this source for studies of historical demography has been recognised, but the occupational information has not been identified and exploited systematically. My Ph.D. project created, from scratch, the novel Yangtze Jiapu Dataset (YJD) with 208,130 occupational observations from 828 counties in the Yangtze Valley, where more than 40% of the national population lived. Comparisons with censuses suggest that the YJD broadly represent the regional population. My project marks the first use of jiapu data to quantitatively estimate the occupational structure of the Yangtze Valley from ca. 1920 to the 1982 census, the first census with reliable occupational data. These new estimates and census data suggest that a substantial shift of the labour force out of agriculture only occurred in the three decades from 1990 onwards with the primary sector share decreasing from 74.6% in 1990 to 19.1% in 2020, which is much later than other changes characteristic of modern economic development, such as the increase in per capita income and the emergence of modern factories with high productivity. The occupational structure series also suggest continuities in the increase in industrial employment across the divides of 1949 when the People's Republic of China was established and 1978 when the 'reform and opening-up' started, which were regarded as political and economic turning points. Comparing the occupational structure and GDP structure data shows that neither the period 1950-1978 nor the period 1978-2020 witnessed the structural change that Kuznets observed in many earlier-developed countries, which he suggested was a concomitant of modern economic growth. The YJD also reveals patterns of by-employment and women's work. Theories of the division of labour, proto-industrialisation, involution, industrious revolution, and economic resilience suggest that by-employment undergoes a continuous decline, or no substantial change, or a rise and then a decline in economic development, but these hypotheses have not been supported with longitudinal empirical data. The YJD, for the first time, provides direct evidence of the prevalence of by-employment over time, which suggests two surges of by-employment among men born between 1821 and 1990, reflecting influences of specialisation, structural change, and institutional changes relating to land and labour. My Ph.D. project also exploited the microdata of the farm household survey led by John Lossing Buck in the period 1929-1933, which suggests that the male by-employment pattern of the Yangtze Valley was similar to that of Yamanashi, Japan, in 1879, conforming to the Asian pattern proposed by Saito and Settsu, in which the majority of cases were of peasant farmers having subsidiary employment in industry, commerce or transport. The by-employment pattern of women in the Yangtze Valley is slightly different in that women devoted more of their working time to domestic industries than to agricultural production. The YJD documents the significant expansion in the diversity of women's work from mostly agriculture and textiles to all occupational categories in the twentieth century, with an increase in the female-to-male ratio for most occupational groups. Data for 42,666 couples show that married women in different sectors and born in different periods had diverse experiences of engaging in the same occupation as their husbands, due to differences in the prevalence of family-based business, marital matching strategies, and political movements. My Ph.D. project also investigated the female labour force participation rate (FLFPR) by combining Buck's survey 1929-1933, population registers in the 1940s, and censuses in the period 1982-2020. Strikingly diverging from the U-shaped profile found in the industrialisation of Britain and the US, the FLFPR in the Yangtze Valley followed an inverse U-shaped profile from the 1930s to 2020, showing the influences of collective institutions, education, and foot-binding. The geographical variations of the prevalence of foot-binding were not recorded completely in archives, but the 'embodied' nature of foot-binding suggests that foot-binding still impacted the participation in market production of women with bound feet in the 1980s. The 1982 FLFPR data, therefore, were used to estimate the geography of foot-binding in the 1930s. Future research that integrates the macro occupational structures, which this project illuminates, and the micro experiences of people's working lives, as recorded in jiapu biographies which have yet to be exploited, will achieve a more comprehensive understanding of the economic and social development of twentieth-century China.

Advanced technologies assist diverse entities in becoming network actors, exchanging resources and co-creating value together to achieve service innovation. However, tensions emerge when multiple actors have different goals and expectations during the service innovation process. This thesis extends the service ecosystems literature by incorporating the evolution of value platforms in the service innovation process over time. The notion of value platforms facilitates our understanding of the dynamic interactions among actors to co-create value for the development of service innovation. The theoretical lens of institutional logics was applied in this study to explore the dynamic resource-related activities that occur as value platforms evolve. This thesis explores the evolution of value platforms embedded in service ecosystems during the service innovation process. It investigates how the resource-related activities evolve in service ecosystems throughout the process of service innovation and seeks to unravel the mechanism of actor interaction in platform-based service innovation. In particular, the study investigates how value platforms embedded in service ecosystems evolve, what tensions arise throughout the evolution due to the multiple institutional logics of the actors within the ecosystem, and how multiple institutional logics are navigated as value platforms evolve. A critical realist approach is adopted to explore the phenomenon of value platform evolution. A process-based single-case study design with two embedded cases is implemented to investigate value platforms embedded in service ecosystems to develop telematics insurance services. The researcher conducted a two-phased data collection to gather semi-structured interviews and participant-generated drawings as primary data from different actors along with archival documents as the secondary data. A realist evaluation enabled the delineation of the five stages that form the building blocks of the evolution of the value platforms. Moreover, an abductive approach identified three types of process-related tensions and three types of navigating mechanisms that emerge dynamically as value platforms evolve. This research offers theoretical contributions to a processual understanding of value co-creation in service ecosystems by explaining the evolution of tensions resulting from co-existing institutional logics and navigating mechanisms inherent in value platforms. It also highlights how regulatory actors affect service ecosystems during the process of service innovation. Furthermore, the study offers practitioners a processual understanding of tensions that occur in the service innovation process, and the approaches to navigating those tensions in service ecosystems during the service innovation process.

Despite using three or more antihypertensive medications, patients with uncontrolled high blood pressure are diagnosed as having resistant hypertension. Persistent high blood pressure can lead to complications such as stroke, heart disease and kidney problems. Currently, this group of patients are not only taking more antihypertensive medicines but also at higher doses. Inevitably, this leads to a higher risk of adverse events. New molecules targeting different sites of action are the focus of new drug development for this condition. In previous work carried out in our research group, a novel phenylethylamine alkaloid, schwarzinicine A, was isolated from a locally grown fig tree, Ficus schwarzii. It has been shown to relax the rat aorta, porcine coronary and pulmonary arteries. One of its relaxation mechanisms was the inhibition of transient receptor potential canonical (TRPC) channels, particularly TRPC3, 4, 5, 6 channels. Theoretically, schwarzinicine A may possess a lower oral bioavailability as it violated Lipinski's and Veber's rules by having a molecular weight (MW) more than 500 Dalton (Da) and 15 rotatable bonds. Furthermore, the yield of schwarzinicine A from natural sources is very low. Hence, N-phenethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FK244) and 1-(furan-2-yl)-N-phenethylpentan-3-amine (PM20), were synthesised based on the pharmacophore of schwarzinicine A. FK244 and PM20 obeyed all criteria outlined in Lipinski's and Veber's rules. This thesis investigated the vasorelaxation profile of FK244 and PM20 in rat isolated aorta and focused on characterising their roles in modulating calcium ion (Ca2+) dynamics. To elucidate the underlying pharmacology of these two compounds, isometric tension recordings were performed on Sprague-Dawley (SD) rat isolated aorta using the organ bath technique. FK244 and PM20 displayed a higher drug selectivity in vascular smooth muscle (VSM) tissues. The findings from organ bath experiments have excluded the roles of FK244 and PM20 in regulating NO, cyclic nucleotides, adrenoceptors, and potassium ion (K+) channels as their vasorelaxant mechanisms. The plausible vasorelaxation effects of FK244 and PM20 via an endothelium-dependent route have also been ruled out. FK244 and PM20 significantly suppressed the aortic contractile response to calcium chloride (CaCl2) in a concentration-dependent manner. They also managed to reduce the vascular tone raised by phenylephrine, potassium chloride (KCl) and U46619. Pre-treatment with FK244 and PM20 attenuated phenylephrine-, KCl-, and serotonin-induced vasoconstriction but had no impact on U46619-induced vasoconstriction. However, in a Ca2+-free environment, they did not affect phenylephrine-, KCl- and U46619-induced contraction. These findings suggested that FK244 and PM20 mainly inhibit plasma membrane Ca2+ channels such as L-type voltage-gated Ca2+ channels (VGCCs) and TRPC channels. They do not influence the internal store Ca2+ release involved in smooth muscle contraction. Incubation with TRPC-selective inhibitors 2-aminoethoxydiphenyl borate (2-APB), Pyr3, Pyr6 and SKF-96365 reduced the efficacy of FK244 and PM20. However, the vascular effects of FK244 and PM20 were not affected by nifedipine and verapamil. These results point to a suggestion that FK244 and PM20 could be modulating TRPC channels in addition to L-type VGCCs. Exposure of FK244 and PM20 to C. elegans did not induce toxicity at low concentration but slightly reduced the nematodes' lifespan at high concentration. Assessment in disease models manifesting hypertension and diabetes have confirmed that the vascular effects of FK244 and PM20 were comparable to that in normotensive SD rats and non-diabetic rats. In addition, fluorometric intracellular Ca2+ recordings were carried out to measure the activity of FK244 and PM20 on TRPC3- and TRPC6-overexpressing human embryonic kidney (HEK) 293 cells. Intracellular Ca2+ measurements in HEK 293 cells have confirmed that FK244 and PM20 blocked extracellular Ca2+ influx via TRPC3 and TRPC6 channels. In summary, FK244 and PM20 displayed significant endothelium-independent vasorelaxation by inhibiting extracellular Ca2+ influx via plasmalemmal Ca2+ channels. One of the targeted Ca2+-permeable channels is TRPC channels, particularly TRPC3 and TPRC6 subtypes. It highlighted TRPC channels as the possible new drug targets in hypertension. TRPC-targeting FK244 and PM20 which prevent vascular contraction, may be developed as antihypertensive agents for resistant hypertension.

This thesis explores changes in the content and material culture of a group of scriptures known as the Foshuo fumu enzhong jing 佛說父母恩重經 (the Sutra Spoken by the Buddha on the Profoundness of Parents' Kindness) during the Tang (618-907) and Northern Song (960-1127) dynasties, examining their relationship to the broader development of Buddhist beliefs and Confucian and other pre-existing non-Buddhist ideas, such as filial piety and ancestor worship. In contrast to previous philological studies that sought to identify the various versions of this scripture and determine the textual origins of its composition, this thesis pays special attention to the objects on which the scriptures are written and inscribed, such as stelae and manuscripts. By giving serious consideration to their inscriptions, material forms, and physical locations against the socio-political backdrop that encouraged their production, this project addresses questions of the uses of the stelae and manuscripts by ordinary, largely unrecorded people in rural localities of Shandong and Dunhuang and the purposes of their patronage.

Covalent conjugation between proteins has been used to develop novel drug delivery methods, enhance therapeutic efficacy, and improve diagnostic sensitivity. Proximity-directed ligation methods enable coupling to unmodified endogenous proteins. A diverse range of proteins contain autoproteolytic domains that cleave at an Asp-Pro bond via an aspartic anhydride intermediate. In this thesis, the anhydride is harnessed as an electrophilic warhead for targeted conjugation. I developed NeissLock, a technology that uses the self-processing module (SPM) of the FrpC protein from Neisseria meningitidis. SPM is fused to the C-terminus of the binder protein so that the anhydride generated upon calcium-induced activation reacts with proximal nucleophiles on the target. NeissLock, using the standard genetic code, enables rapid and specific coupling under mild conditions. I discovered that the FrpA SPM variant has an enhanced activation rate compared to the first-generation NeissLock. I developed a bacterial surface display system for directed evolution of SPM, towards improving the cleavage yield and stability of the domain. Finally, I established the split SPM system by splitting the domain into 2 fragments to provide another level of control over SPM activation. The fusion of SpyTag003/SpyCatcher003 to the split SPM fragments increased the coupling efficiency. Split SPM facilitates the mammalian expression of binder-SPM fusions, broadening the applicability of NeissLock. I fused various human red blood cell-binding peptides to SPM to test for coupling to human red blood cells. Covalent conjugation of therapeutic proteins to red blood cells using NeissLock would increase the stability of coupling compared to non-covalent methods, potentially enhancing drug delivery using red blood cell carriers.

Dengue fever causes mortality and morbidity worldwide which is a major concern to governments and the World Health Organization (WHO). It was reported that carpaine, the major active compound extracted from papaya leaves, contributes to the anti-thrombocytopenic activity. Hence, carpaine plays an important role in treating dengue patients by raising the platelet count in the patients' blood. However, carpaine in papaya leaves could degrade easily when exposed to heat and sunlight during processing and storage. There is no literature reporting on the processing aspects (e.g., preparation, drying and storage) of papaya leaves and the leaves extract to date. This could possibly be due to papaya leaves have no commercial value and the leaves are usually treated as waste. Therefore, this thesis will focus on the effects of drying conditions on drying kinetics, product quality and retention of carpaine in papaya leaves. Extraction and quantification of carpaine from different parts of papaya leaves (young and old) and stalks were carried out. Pale yellow carpaine crystalline powders were successfully extracted and confirmed to have high purity (>95%) by 1H and 13C NMR analyses. Unblended freeze dried samples from young papaya leaves extract showed the highest amount of carpaine, total polyphenol content and DPPH free radical scavenging activities. It is thus recommended to use young leaves to extract carpaine for future drug development in dengue treatment. The drying kinetics and drying rates of papaya leaves using different drying techniques such as hot air drying (60°C, 70°C and 80°C), shade drying and freeze drying were investigated. Typical exponential falling trends were observed, which can be best explained by Fick's second law of diffusion. The fastest drying rate was observed at high temperature (80°C), followed by at lower temperatures (hot air drying at 60°C and 70°C, and shade drying at averagely 27°C). By using the general solution of Fick's second law and Arrhenius equation, the effective diffusivities were determined in the range of 2.09 × 10-12 m2/s to 2.18 × 10-12 m2/s, and the activation energy required to initiate moisture diffusion was determined at 2.11 kJ/mol in hot air drying within 60°C to 80°C. Besides, the effects of drying techniques on carpaine retention and antioxidant properties of papaya leaves were investigated to develop a preparation protocol that produces papaya leaves extract with high carpaine retention. Hot air drying at 60°C, 70°C and 80°C are not recommended for the preservation of carpaine in papaya leaves as carpaine is a heat sensitive bioactive compound. Results showed that the carpaine retention in hot air dried samples were significantly lower (p < 0.05) than freeze dried and shade dried samples. It is recommended to use freeze drying to remove the moisture in the papaya leaves as it showed the highest retention of carpaine and antioxidant activities. The knowledge on the stability of carpaine during storage is vital as the raw materials used would be mainly in dried form which will be stored in bulk quantity during commercial operation. Studies show that the Weibull model produced the best graphical fit in describing the degradation kinetics of carpaine in all dried samples (freeze dried samples, hot air dried samples at 60°C and 70°C, and shade dried samples), except for hot air dried samples at 80°C, which could be best described by the first order model. Freeze dried samples showed the highest half-life (51.20 months) among all the dried samples. It is thus recommended to select freeze dried samples for extended storage purpose as it is more stable as indicated by the lowest rate constant and the highest half-life.

Sustainable and low-cost materials have attracted extensive research attention for new generation solar cells. With the emergence of hybrid lead-halide perovskite solar cells, the last decade has witnessed an ever-increasing power conversion efficiency rise in the field of printable photovoltaics. However, major issues in lead-halide perovskite solar cells research concern the toxicity of lead and the long-term device stability, which potentially hampers the large-scale manufacturing process for the next stages of development. Meanwhile, tedious synthesis routes and the expensive cost of the commonly used hole transport materials (HTM) further slow the commercialisation. Therefore, alternative lead-free absorbers with long-term stability and low-cost HTMs are needed. This thesis starts with two inorganic Bi-based absorbers, Ag3BiI6 (Chapter 3) and NaBiS2 (Chapter 4). Although the silver rudorffites (Ag-Bi-I) family has been widely reported with promising efficiency of up to 5.44% in the conventional p-i-n solar cell configurations, no previous research has been carried out using these in the fully printable triple-mesoscopic solar cells (TM-SC). In Chapter 3, the study sets out to examine the feasibility of using Ag3BiI6 as an absorber in TM-SC and to investigate the effects of pre-treatment (e.g. biPY, 4-tBP, CPDT-1 and N719) on pore-filling and overall device performance. The best as-prepared device achieved 0.33% efficiency. To improve the device performance, CuSCN was added as post-treatment to enhance the hole extraction, boosting the power conversion efficiency (PCE) to 0.74% after ageing. Another Bi-based material, NaBiS2, has not previously been studied as a light absorber, whereby most studies have focused on the photocatalytic application. Previous theoretical studies highlighted that NaBiS2 could potentially achieve better performance than the analogue AgBiS2, which has been reported with 6.3% efficiency. In Chapter 4, the overall aim of the project is to apply a straightforward xanthate decomposition method to obtain NaBiS2 thin-films. Although this study presented here confirmed a largely phase-pure and fast photo-response of NaBiS2 films, the device performance in conventional n-i-p solar cells was poor. By introducing the xanthate decomposition method in TM-SC, the as-prepared device achieved 0.01% efficiency and improved performance (0.04%) was observed after one-week ageing. This thesis also includes a study of low-cost HTM-1,3,5-tris(2'-(N-phenothiazylo)phenyl)benzene (TPB-2-TPTZ) that has been previously reported as an alternative for commonly used Spiro-OMeTAD. Despite promising properties held by TPB(2-TPTZ), the device performance was below expectation in previous studies. In Chapter 5, the aim is to determine what limited the solar cell efficiency and whether changing the dopants (e.g. NOBF4 and CuBr2) and using polymer (e.g. PTAA and PMMA) additives could improve the film quality and thus the conductivity. It is evidently clear from the findings that the previously reported low efficiency is largely affected by the low conductivity due to poor film quality. In this study, although this was still lower than state-of-the-art HTMs used in perovskite solar cells, with the combination of 22%-CuBr2 and 14%-PMMA additives, TPB(2-TPTZ) exhibited 10 times higher conductance compared to conventional Li-TFSI doping.

Over the last few decades, rapid technological advancements have raised challenging and pressing questions for education. Among them, the critical competencies required for a future-ready generation are continuously debated. Computational thinking (CT), entailing a set of cognitive skills important for programming and problem-solving, has emerged in the literature as such an essential competence domain. As a newly emerging construct, there are two fundamental questions in the CT literature needed to be illuminated: what is the nature of CT and how is it evidenced? In other words, is CT a domain-specific skill, a domain-general skill, or a competency reflecting a combination of both? These questions are explored through three empirical studies, which address different aspects in conceptualization and assessment undertaken by different methodological approaches. Throughout the thesis, I redefine the understanding of CT from a traditional, common domain-specific perspective (e.g., programming-centric view) by proposing a hybrid account that perceives the construct as a complex competence domain. In doing so, my theoretical proposition of CT competency bridges domain-specific and domain-general perspectives, arguing it encapsulates both programming and problem-solving skills. Starting with conceptualization, Study 1 investigates teachers' views using a text mining approach, shedding light on the nature of CT and appropriate assessment design. The results supported my design of a technology enhanced assessment of CT competency, Computational Thinking Challenge (CTC). The CTC adopts an integrative assessment design, which includes multiple contexts, formats, and problem types in reflecting the diversity of CT competency. Hence, it is critical to address the issue of whether the diversity of the tool impacts its quality. For this, Study 2 conducts a rigorous psychometric evaluation using a Rasch model from an item response theory approach. Extending from this, Study 3 examines the structure of CT competency, using a multidimensional item response theory approach, to investigate the structural validity and item quality of the CTC. In addition, a bi-factor model is specified to test my proposed theoretical model that consists of a general CT competency factor and two specific factors in programming and problem-solving. Together, the studies provide supporting evidence to my theoretical proposition and help elucidate the nature of CT as a competence domain. The studies also demonstrate the promise of adopting an integrative assessment design in evidencing CT competency through the CTC. In short, this thesis addresses questions that bridge conceptualization and assessment: (1) What is CT competency? (2) How should it be evidenced? and (3) Is the measurement method reliable and valid?

At the beginning of this present research, I had observed that the concept of engagement is receiving increased attention because it offers considerable benefits for research and classroom practice. However, compared with the rich body of research on work engagement and student engagement in the past decade, few studies have investigated teacher engagement, particularly in teacher CPD in my research context - China. Current research suggests that the potential of understanding teacher engagement in CPD has not yet been fully realized. Thus, the purpose of this research was to explore and identify distinct profiles and factors of teachers' engagement in professional development, and further, to investigate whether the effects of these engagement factors vary in relation to different forms of CPD activities. The data above were gathered from teachers in China through two studies using four collection instruments: two questionnaire surveys and two semi-structured interviews in a mixed-methods research design. The results of the current study have identified three teacher engagement profiles, Less Engaged, Moderately Engaged and Highly Engaged, in terms of varying degrees and levels of engagement in CPD. The factor analysis has revealed that four factors predict teachers' engagement in their professional development: Cognitive Factors, Instrumental Factors, Self-Actualizing factors and CPD Cultural Factors. Furthermore, teachers' years of experience and education-levels are related to all four instrumental factors, with teachers in their late professional career phase (21+years of experience) and teachers with only 'associate' degrees reporting less influence exerted by instrumental factors on their engagement in CPD. Female teachers had greater engagement and reported greater impact than male teachers on teaching practice when it involved peer observation with feedback. Along with these results, female teachers also reported greater influence of two of the Self-Actualizing Factors: peer feedback and public recognition. In order to better understand the internal relationship between these factors, I propose a factor-based model of teachers' engagement in professional development. Moreover, I have investigated the variation in the perceived impacts of these identified factors on facilitating teachers' engagement in three different formats of CPD activities in schools in China (Teaching Research Teams [TRT], Teaching Research Groups [TRG] and Research Lesson Study [RLS]). Results revealed that respondents were more driven by identified factors to engage in RLS and TRG but displayed much lower engagement in TRT. In specific, the combination of Intellectual and CPD Cultural Factors was most likely to predict respondents' engagement in the three CPD activities. Self-Actualizing Factors most strongly affected teachers' engagement in RLS. Instrumental Factors were found only to exert strong effects on novice mentee teachers and some TRG group leaders, but not on other TRG members.

Discrete or distinct element methods (DEM) are now using realistic particle shapes but consequently the correct contact mechanics are also now required. There is some existing work for the contact behaviour for sands but only a little on crushed rock materials (ballast and rockfill). Therefore, an inter-particle loading apparatus was designed and constructed to test ballast particles. It has a 3-axis control of forces and displacements, and is able to measure the displacements accurately with capacitive proximity transducers, and its high accuracy allows to resolve stiffness precisely. The stiffness of the apparatus was the key issue to make sure the compliance corrections were not large so careful calibrations and modifications were carried out throughout the development. The tested material in this research was granite, which is a typical railway ballast in the UK. The coefficient of interparticle friction (µ) was measured along with its evolution with cyclic loading and typically tended to stabilise at about 0.6-0.85 for dry samples. Continued sliding generated a large amount of powder, of which the mean size was 25µm. However, the roughness of the interface reduced. The µ values for the linear shearing before cyclic loading were lower than those for the first cycle (about 0.25-0.75). Water immersion has a clear effect on µ values but not the load level. Loading fresh contacts or loading old contacts made no difference to the µ values and there was no rate of sliding effect. Both normal and tangential load cycling gave hysteresis loops and the loop size increased with the load. The normal and tangential contact stiffnesses are highly non-linear and much softer than Hertz-Mindlin elastic solutions. Normal loading could be fitted with a Hertz model accounting for surface roughness but only using the whole particle size not the measured contact radius. However, these conclusions are only validated for granite and it would be interesting to see whether they are repeated for other ballast materials.

Schooling is often seen as a promise for brighter futures and better life opportunities; however, these potential outcomes cannot be realised if schooling cannot even be accessed in the first place. While the availability and proximity of schools and educational institutions are undeniably important, it does not necessarily imply access as it is conditioned by various factors at the individual, household, community and institutional level. Based on eight months of ethnographic fieldwork in Delhi, my thesis explores the sociocultural factors which influence access to schooling for children and youth from waste picker families, whereby access entails not only initial enrolment but also progression, regular attendance and meaningful learning which has utility. I also examine how schooling might translate into better futures, and the sort of mobilities which it could lead to. This research is set within the context of schooling as a strategy to enhance livelihoods, especially during a time when waste pickers are increasingly excluded from urban development policies that seek to transform Delhi into a world-class, modern and clean city. Using interviews, informal discussions and participant observation, I explore how aspirations and perspectives towards schooling are shaped by the individual life experiences of children and parents. I consider how access is enabled and disabled by community leaders and NGOs, and how schooling informs the identity-building processes of waste picker children and youth. My findings show that parental aspirations and their perceived value of schooling have an important influence on how they negotiate access to schooling for their children. NGOs play a crucial role in this process, as they empower parents to navigate misrecognitions and acts of symbolic violence from community leaders and bureaucratic procedures that hinder schooling access. I also show how schooling enables one to "become somebody", which encompasses this sense of control and authority over one's self-identity, mind set and development. Through this thesis, I argue that for schooling access to be meaningful, it should be understood in relation to the lived realities of waste picker families - their livelihoods, experiences, relationships and their aspirations. For children and youth, aspirations not only mean what they want to become, but more importantly, who they want to become. Given this, it is important to reflect on the politics of care, and what it means to act in the best interest of the child, so that better and more effective support can be provided to children and youth in their personal journeys.

The recognition in 2011 of the extraordinary Shimao site (ca. 2300-1800 cal. BC) in the North Loess Plateau as late Neolithic China's largest stone fortification, has overturned our understanding of the development of complex societies in northern China. The 400-hectare stone fortification of Shimao lies at the heart of the climate-sensitive region (hereafter the Shimao region), which located at the junction of modern-day south-central Inner Mongolia, northern Shaanxi and northern Shanxi, featuring numerous stone fortifications during the period ca. 2800-1300 cal. BC. The settlements in this region have the unusual combinations of herd animals, millet, ceramic tripods, and high-valued jade and bronze artefacts, suggesting a development in wealth and social economy. The central question addressed in this thesis is how and why Shimao, along with the surrounding settlements, flourished in the south sector of the region. Currently, we cannot determine what drove the growth and complexity of Shimao and other similar sites because the development process in demography and social economy in the Shimao region is poorly understood-the problem has not been interrogated from a wholistic regional perspective. A more precise chronology is also required to provide context to identify changes over time and space. The first problem addressed is a review of all the radiocarbon dates from the published literature; these dates are scrutinised for quality and then subjected to Bayesian modelling for a firmer chronology. The other sources of information-settlement size and distribution, economic basis as judged from faunal abundances and mortality profiles, and ceramic tripods associated with food preparation-are considered within this chronological framework in order to identify new development during the Shimao period. The findings suggest that population shifted and became concentrated in the south sector of the region, with the development of a new socio-economic network, which contained Shimao and the surrounding sites. Within this network, Shimao acted as a ritual centre with a highly concentrated population and attracted people from the surrounding area; meanwhile, people in this network adopted and used herd animals and new forms of ceramic tripods in their own ways. The findings also suggest that the form of urbanism developed at and around Shimao is unique: a central role can be seen at Shimao in social and ritual contexts, but centralisation and clear urban-rural relations among sites cannot be identified in animal and ceramic economies. Both the pulling factor from Shimao and the climate factor, which may have introduced indirect and gradual influences on human decision and activities, were significant for the success of Shimao and the wider region.

This thesis summarises the photoluminescence results I have taken on the three different nanostructures of CsPbBr3 perovskite. Due to their microscopic dimensions, interesting physics phenomena under the fields of optical science and quantum mechanics have emerged. With the aid of a confocal micro-photoluminescence setup, detailed sub µm-level features can be retrieved directly for analysis. Although the three topics root from separate branches of specific physics fields, they all demonstrate how this system can be exploited as a general tool for examining the time-integrated and dynamical behaviours. Therefore, the thesis helps build the necessary knowledge for adaptation into different scenarios and external modification for a more specialised measurement. On the other side, much of the content has been devoted into systematic explanation of the relevant concepts in a self-contained fashion. These include the discussion on lasing phenomenon, Gaussian modes and triplet state. These recap or exposure to the different fields will be sufficient for the reader to understand the rest of the content. The results are selected from the three papers I have written. The first topic is on confined Gaussian modes in CsPbBr₃ microcavities. These cavities are naturally formed by the even smaller building blocks of quantum dots. The emission observed depends upon the collective behaviour of the zero-dimensional objects. The second topic is relevant to triplet state and resonant pumping of the CsPbBr₃ nanocrystals. Doubly degenerate states associated to the tetragonal phase of the crystal have been presented. A resonantly optimised lasing effect then builds on this triplet signal and shows great potential for device applications. The third topic is about passivated CsPbBr₃ nano/micro-rods with Pb(OH)₂ cladding. A temperature-tolerant emission and bright stimulated emission from defect sites have been demonstrated. All the three topics have illustrated the potential towards modern optoelectronic applications and the underlying physics can provide further inspiration from a slightly twisted angle for the future structure design. In the appendix, a guide to the mapping software is introduced. This is a handy tool for analysing the complicated map data, which can be a crucial part of the PL study. The software provides control over the map position and wavelength, as well as a diffusion analyser. It also incorporates a zooming function such that local intensity rescaling is possible.

Timber has become one of the popular choices as a sustainable building material, and with the increase in timber building height, the problem caused by wind load becomes remarkable. Most research focused on the ultimate structure performance under wind load or vibration under cyclic shear force due to dynamic wind load. However, a lack of research on the serviceability of timber wall connections under out-of-panel load caused by dynamic wind pressure may lead to underestimating damage to timber structures. Therefore, this study investigates the fatigue performance of connections for plug-in timber panels under out-of-panel cyclic load caused by wind. The study first developed a new method to design loading sequences for a lab test, to analyse the joint fatigue behaviour under wind load. This research focused on the angle bracket connection system with fasteners. Compared with the testing sequences from other building codes, the newly developed process is more logical and can save testing time. The high-cycle fatigue testing results proved that wind load could degrade stiffness of timber wall joint with an angle bracket system but did not cause the connection system failure or material damage. Additionally, with the increase in building height, stiffness reduction increased. The angle bracket connecting system can connect timber and concrete but selecting the angle bracket type is essential. Different connecting details were tested. The results demonstrate that changing nail pattern or angle bracket size can influence the cyclic fatigue performance of timber wall joints. By applying the digital image correlation (DIC), this study indicates that the cyclic loading mainly affects the mechanical properties of joints by affecting the embedment of fasteners rather than the strain of the angle bracket. This study then extended the investigation to the life-cycle environmental impact of timber building. Results pointed out that neglecting the energy or material used for joint timber maintenance can cause at least 20% underestimating the embodied carbon.

The core feature of human heritable genome editing ("HGE") is that any modification made on the germ cells (sperms or eggs) or early human embryos is likely to be passed down to subsequent generations. This feature makes the use of this technology highly controversial. Thus, there is a need to adopt a suitable approach to consider future children who are going to live the consequences of this technology. Taking a child-centred perspective, this thesis explores two main concerns: first, whether, and to what extent, the act of HGE is ethically acceptable; and second, how should HGE be regulated if it is deemed ethically acceptable for reproductive use. More specifically, it examines how a child-centred approach should be adopted in answering these questions. This thesis first examines four child-related arguments commonly raised in the existing HGE debate, including the non-identity problem, the open future argument, the purported right to non-modified genomes, and the proposed long-term follow up system for the resulting children. It argues that the existing arguments and proposal have failed to appropriately consider (future) children's interests mainly because there is (1) a lack of solid theoretical framework to justify the recommendation commonly made for a health-related use of HGE, and (2) a lack of detailed analysis on an important but often overlooked concept in the HGE debate, that is the concept of "identity". In order to fill these gaps, this thesis explores the capability approach and argues that Jennifer Ruger's health capability paradigm provides a good philosophical framework in understanding why "health capabilities" can justify and more importantly, also limit the health-related use of the technology. Additionally, this thesis analyses the concepts of "identity" and argues for a multi-faceted understanding of "identity" with narrative identity to be given the greatest weight in the ethico-legal considerations of HGE.

Cholangiocarcinoma (CCA) is cancer of the bile duct that only has a few treatment options, typically with poor prognostic outcomes. The Proline-Rich Homeodomain protein (PRH), also known as haematopoietically expressed homeobox (Hhex), is a transcription factor that regulates liver and bile duct development. PRH is not expressed in normal bile duct cells but this protein is highly expressed in CCA cells. Using a combination of overexpression and knockdown experiments, PRH was shown to increase cell proliferation, migration and invasion in tumour cell lines. Similar results were obtained in immortalized AKN-1 cells and also in primary biliary epithelial cells. In these cells PRH overexpression also led to the initiation of epithelial to mesenchymal transition (EMT) and anoikis resistance as well as increased cell proliferation and invasion. Gene Ontology and Gene Set Enrichment Analysis of RNA-sequencing data from cells with altered PRH levels reveal that in all cell types PRH regulates multiple signaling pathways and that key genes involved in the Notch signaling pathway, the cell cycle and EMT are regulated by PRH. CCA cells with elevated PRH expression were found to be more sensitive to the CDK4/6 inhibitor Palbociclib as PRH controls the cell cycle through regulation of multiple cell cycle genes including CCND2. Drug screening with a drug repurposing library was performed to identify novel drug treatments for CCA and several repurposed drugs that show a stronger cytotoxic effect when combined with Palbociclib were identified using cell viability assays. This thesis therefore reveals that PRH protein is an important oncoprotein in CCA and that this protein may play a role in initiating CCA and in driving cancer progression and identifies new drug treatment options.

How do latecomer firms from emerging countries compete with incumbents from developed countries in digital industries and what innovative capabilities do they build in order to succeed? The convergence of digital technologies across different disciplines has accelerated technological change and created numerous opportunities, yet existing catch-up literature is not sufficient to explain how latecomer firms from emerging economies with lagging digital technologies have caught up. Drawing upon a qualitative case study of the digital games industry, especially in China and Taiwan, the focus of this research is to explore how the feature of digital product architecture influences the mechanisms of catch-up and capability-building of latecomer firms in emerging economies and to develop a deeper understanding of the relationship with the institutional settings in which they are embedded, and successful catch-up strategies. Meanwhile, changes in industry leadership cannot be neglected because catch-up is not only about catching up, but also the establishment of industrial leadership. This would help to place the concepts of catch-up and capability building in a broader context of competition and industry leadership. The analysis is based on in-depth semi-structured interviews with 62 senior managers (founders, CEO and top-level managers) from firms, and experts (academics, industry experts and government representatives) in China and Taiwan, and triangulates through content analysis of government and company reports and auxiliary data sources. This thesis makes five contributions. First, it develops an integrated analytical model to explain the relationship between technological capability-building, catch-up, and the change in industry leadership, by carefully describing the changes of industry leadership in the world digital games industry and exploring the difference between the behaviours and strategies in latecomer firms in emerging economies and leading incumbent firms in developed countries. Second, this study contributes to our understanding of the industry leadership change in the digital sectors, identifies the common determinants affecting the successive catch-up cycle, and further conceptualises the historical conditions of different countries and the effectiveness of catch-up to provide a more abundant, dynamic picture. Third, this thesis contributes to catch-up literature by revealing how technological regimes in the digital sector affect learning, capability-building and the catch-up processes of latecomer companies in emerging countries. Fourth, this thesis contributes to the learning and catch-up framework by demonstrating the potential of latecomer companies in emerging countries to improve their technical capabilities by their prior industry experience and skills transfer, and the final-end buyers as the knowledge base. Finally, this thesis contributes and extends the literature on the role of institutions in helping latecomer companies to achieve high levels of catch-up performance.

Thermal imaging devices based on Complementary Metal-Oxide-Semiconductor (CMOS) and Micro-Electro-Mechanical System (MEMS) technology are widely used across consumer and industrial applications. The combination of CMOS and MEMS technologies allows for the production of devices with high performance, good reliability and consistent reproducibility. Additionally, these technologies allow devices to be manufactured at low cost and a high volume. There are several types of thermal sensing technologies, however, this thesis mainly focuses on 8×8 thermopile based Focal Plane Arrays (FPAs). The core principles governing the function of thermopiles are based on the Seebeck effect. In this thesis, the structure and fabrication process of thermopile FPAs are described and discussed. The thesis describes the functionality of the array chip and introduces a new experimental technique, called the bi-directional electrical biasing method, which was applied to obtain the device's responsivity and crosstalk measurements. Compared to traditional measurement approaches using laser sources, this novel method significantly reduces the complexity of the experimental setup, as no external laser source is required. The crosstalk of the 8×8 array is ~2.69% and the responsivity is ~73.1 V/W. A detecting system using a larger array chip was designed, created and successfully applied in a series of experiments that involved gesture recognition and people counting. In order to enhance the performance of the current array device, a 3D simulation model based on the Finite Element Method (FEM) was built using the COMSOL Multiphysics simulation tool. The numerical model was validated by comparing the model's simulated values for responsivity, crosstalk and temperature distribution with experimental results. The difference between the simulations and experimental results was < 5%. With the aim of optimising various trade-offs, modifications in heatsinking track widths/materials, additional air gaps between pixels, different packaging and different pixel sizes were assessed using numerical models. A design with copper heatsinking tracks and air gaps showed the best results, achieving an increase in responsivity by 6.4% while simultaneously reducing crosstalk by 65%. In addition, the vacuum packaging can reduce the crosstalk to less than 0.7% (only 0.2% in the model with copper tracks) and increase the responsivity to > 90 V/W in the model with tungsten tracks. A 32×32 array design demonstrates the smallest pixel size that can be achieved based on this thermopile array design. The 32×32 array design increased responsivity to ~77.18 V/W and crosstalk remained < 4%. Crosstalk rose sharply to >6% when the pixel size was reduced further in a 64×64 array design, at this level of crosstalk, image quality is likely to be significantly affected. Future work may focus on the implementation of carbon nanotubes or novel 3D thermopile designs. Carbon nanotubes, when deposited over the array chip, could enhance the absorption of IR radiation. While new thermopiles employing a 3D design could dramatically reduce array size and potentially achieve a fill factor of 100%.

There are multiple biofunctional peptides in amphibians which assist in their survival in diverse environments. Many bioactive peptides from this source were found to have the potential to be developed into new drugs in the future. In this thesis, two peptides found in frogs and their analogues exhibited various bioactivities, namely, antimicrobial, anticancer, myotropic activity upon smooth muscle and so on. A novel bioactive peptide, QUB-2849, was first identified from the skin secretions of the blue-sided leaf frog, Agalychnis annae, by use of molecular cloning. It was found to be equipped with antimicrobial, anticancer and low haemolytic activity. Targeting the truncation of the N terminus of the original dermaseptin peptide, QUB-1875, QUB-1642 and QUB-1159 were designed and synthesized. The truncation could maintain the antimicrobial activity and weaken the haemolysis. Then, analogues, QUB-1159, QUB-2132 and QUB-2683 were designed and their anticancer activity was assessed as compared with that of QUB-2849.This was to ascertain if there was a possibility to develop an excellent anticancer peptide by using a fusion membrane-lytic peptide with a typical sequence of the C-terminus of a dermaseptin peptide or a known anticancer peptide fragment PMI, targeting p53 site. Only natural peptide, QUB-2849, had selective anticancer activity and its anticancer mechanism against the prostate cancer cell line, PC-3, was found to be membrane lysis. Another peptide, DK22, from the brain of Oki Tago's brown frog, Rana tagoi okiensis, and its truncated form, QUB-1228.5, with the middle disulphide bonds and their respective non-oxidized analogues, QUB-2490 and QUB-1230.5, were studied to explore their bioactive functions. These peptides showed varying degrees of myotropic effects on rat bladder smooth muscle relaxation which might be related to potassium ion channels. QUB-1230.5 and QUB-2490 could influence inflammatory cytokine production in rat macrophages, which might be related to their antioxidant activity.

This thesis examines the synthesis of novel acyclic silylenes with amido, boryl, gallyl and/or boryloxyl substituents, and their reactivities towards small molecules such as H2 , CO2 , H2O, NH3 etc. The silylene systems were also used as precursors for compounds featuring silicon-heteroatom double bonds, with a focus on the attempted synthesis of molecules featuring a Si=O moiety (silanones). Chapter 2 discusses the reactions between the gallyl anion [(DippNCH)2Ga] - and Si(II) precursors such as IDipp·SiCl2 and (NTMSDipp)(IiPrMe)SiCl. While an unexpected silyl anion formed when IDipp·SiCl2 is used, a novel NHC stabilized silylene can be synthesized by metathesis between [(DippNCH)2Ga]- and (NTMSDipp)(IiPrMe)SiCl. The gallyl-substituted silylene reacts with N2O, however, only a silyl migrated product can be isolated instead of the expected silanone. The reaction between Cy2NSiBr3 and [(DippNCH)2B] - , in attempt to install an amido substituent on a potential silylene system without a labile N-SiMe3 moiety, results instead in a C‒H activation product. Chapter 3 reports the synthesis of a novel bisboryloxysilylene, together with its heavier Ge, Sn and Pb congeners (the latter in collaboration with Dr Ying Kai Loh). Structural parameters of these tetrylenes obtained by X-ray crystallography, including the E‒O, O‒B bond distances and O-E-O, E-O-B bond angles (E = Si, Ge, Sn or Pb) show a trend consistent with expected periodic trend for group 14 elements, resulting from relativistic effects and increasingly poor s-p mixing on descending group 14. Further investigation involves studies of the reactivity of the bisboryloxysilylene fowards small molecules possessing an E‒H bond (E = H, N or O). Although no reaction is detected with H2, the silylene is able to activate the polar E‒H bonds in water, ammonia and tert- butyl amine. Such processes most likely occur through a three-molecule transition state as shown by DFT calculations. Chapter 4 explores the possibilities of synthesizing Si=E (E = C, N, O or Se) containing compounds using the bisboryloxysilylene as the precursor. The reaction between the silylene and N2O generates the first example of a silahyponitrite, which can be regarded as a masked silanone (by N2O) as the bound N 2 O can easily be substituted in reactions with CO2 and Ph3P=O. When the silylene is treated with an excess amount of selenium, a novel tetraselenosilolane can be isolated. Three out of the four selenium atoms in this compound can be removed by adding Ph3P to generate a silaselenone. Attempts have been made to synthesize a Si=N or Si=C double bond. In the former case Me3SiN3 was used as the source of Me3SiN. However, this reaction only gives a two-fold addition product, a silaazide. In the latter case Ph3P=CH2 was utilized to act as a :CH2 transferring agent. The reaction proceeds instead via a [4+1] cycloaddition process, yielding a dearomatized silaheterocyclic compound.

Mitochondrial dysfunction has a recognized role in the pathophysiology of neurodegeneration, including ischemic stroke and Alzheimer's disease (AD). Compelling evidence shows that leptin prevents neuronal apoptosis and enhances cognition in AD models, and a bioactive fragment, leptin₁₁₆₋₁₃₀, mirrors the neuroprotective actions of leptin. However, their effects with relation to mitochondrial function in neurodegeneration and the receptor binding of leptin₁₁₆₋₁₃₀ remain largely unknown. Based on a combined glucose-serum deprivation (CGSD) model of ischaemic stroke in human SH-SY5Y cells and an Aβ₄₂-treatment model of AD in mouse hippocampal HT-22 cells, it is shown within the thesis that leptin alleviates excessive mitochondrial fragmentation by inhibiting fission protein Fis1 and increasing fusion protein Mfn2. Leptin improves mitochondrial function through enhancing mitochondrial membrane potential and inhibiting monoamine oxidase (MAO) that is involved in the production of reactive oxygen species (ROS). Furthermore, it is found that 17β-HSD10 is a molecular target of leptin in mitochondria by showing that leptin inhibits both the expression and activity of 17β-HSD10. Leptin and the inhibition of 17β-HSD10 rebalance energy metabolism through improving neuronal glucose uptake. Notably, leptin-mediated inhibition of 17β-HSD10 is associated with better episodic memory. Both leptin and leptin116-130 decrease ROS generation and promote neuron survival in oxidative stress-induced wildtype neurons, whereas only leptin₁₁₆₋₁₃₀ retains its neuroprotective effects in leptin receptor (ObR) knockdown neurons, suggesting that actions of leptin₁₁₆₋₁₃₀ are in a ObR-independent manner. In conclusion, leptin's established neuroprotective actions may, at least in part, be facilitated through regulating mitochondrial function and morphology. Inhibited mitochondrial 17β-HSD10 contributes to leptin's procognitive role. The receptor binding of leptin₁₁₆₋₁₃₀ is not restricted to the ObR activation, suggesting the potential application of leptin₁₁₆₋₁₃₀ in leptin resistant individuals. These findings provide more robust evidence to support that leptin system is a potential therapeutic target in AD.

Online learning has been reported to be increasingly used within Chinese higher education. The rapid expansion has created a problem that it's difficult to carry out real-time learner interaction among a great number of students. The pure online instruction made the existing problems in university EFL teaching even worse, such as 'teacher-centred' instruction, student's low learning motivation and low level of class participation. There is a need to develop pedagogies in EFL teaching in China to meet expanding demand and solve the problems. Therefore, this study aimed to explore the integration of cooperative learning (CL) into online EFL curriculum to facilitate learner interactions, bring about meaningful learning together and research its influence on learner writing proficiency. To be specific, it was to explore whether online cooperative learning (OCL) with elements of Social Interdependence Theory (SIT) could actually manifest during learning and teaching online and whether there may be initial evidence that OCL could be effective at raising EFL learners' writing attainment. A researcher-designed online writing curriculum was delivered to 17 university students in nine weeks, once per week for 90 minutes each session. The course, named Step by Step University Writing Skills, was composed of 12 topics, aiming to develop learner's skills of writing a sentence, writing a paragraph and writing an argumentative essay step by step. Learning tasks using CL techniques Jigsaw, Think-Pair-Share (TPS), Random Reporter, Assigning group roles (AGR), were assigned in each session for the learners to practice the teaching contents in groups. The Questionnaire-Scale of 'Learner Experience & Perception on Cooperative Learning' was used to assess the learners' prior knowledge of CL, their previous experience of CL and their attitudes toward CL before they took the OCL course. Learners' writing proficiency tests were taken twice before and after the course as the pre-test and the post-test to measure the potential impact of OCL pedagogy iii (notwithstanding that this was a modelling trial and did not use a control group). Learners' online cooperative interactions were video-recorded, transcribed and analyzed qualitatively to investigate the evidence of SIT in CL online. A post-course questionnaire was given after the intervention to find out learners' perceptions of the impact of CL implemented in the study. As this was a small modelling trial, the study was not powered to detect the effectiveness of the intervention. Rather, it was to explore the feasibility of CL pedagogies be used in online curriculum for EFL learners. The analysis showed that CL with elements of SIT can be identified in learner online interactions. Learners' writing attainment was improved after the course. The conclusion was that CL activities could be designed into an online course with EFL students; students reported that using the OCL pedagogies was an acceptable way to learn; that the technique could be scaled up to a larger sample. The study provided evidence on how OCL worked and how the online pedagogy was structured for CL to work. It presented a good theoretical model for planning and structuring CL activities online with EFL students. The study offered a basis to conduct a larger effectiveness study of the OCL. The findings in this study contributed to the existing literature on online cooperative language learning and CL in EFL instruction. Besides, it combined the cooperative skills into the curriculum contents, which contributed greatly to the higher education practice from the social dimension. In doing so, it offered an opportunity to make a positive contribution to the higher education reform in China.

It is noted that in the field of research on discourse and education, most studies of teaching and learning have focused on discrete elements: classroom discourse; written feedback; pre-class reading; note-taking, etc. For some research questions, such an approach is adequate and productive. However, the present research utilizes an analytical framework developed from an ecological perspective on learning, language and communication, which foregrounds a new line of investigation that builds on and can complement the important work on discrete components of teaching and learning. By using an ecological perspective on communicative interaction, this study describes and analyses the complex system of communication in teaching and learning of two different disciplines in a UK Higher Education Institution (HEI). The ecological perspective views communication, of which language is a major medium and which is central to teaching and learning, as a system occurring at several levels of complexity simultaneously. Learning in a HEI module is viewed as complex and integrated, involving a range of interrelated communicative events that take place over an extended period around an activity. This study therefore provides the detailed methodology of using the ecological perspective of learning, language, and communication to investigate how knowledge is constructed in humanities and in social science iii modules in a HEI. In addition, the findings reveal important but not immediately obvious aspects of the communication processes and identify communication problems that can be addressed to facilitate learning. Specifically, mistakes or misunderstanding in the assignments identified by the teachers were traced to the academic references, reading notes, lesson talks, class notes, and supplementary course materials, raising awareness to the complexity of the communication process in the learning journey. Misunderstanding or miscommunication of subject knowledge can take place at various stages in the process. Correspondingly, certain strategies are suggested to help at specific junctures in addressing the problems and facilitating learning.

Low technology readiness levels (TRL) technologies are attractive to the aerospace industry because their maturation cycles can happen simultaneously with the development lifecycle of the aircraft. However, due to the limited knowledge about a new technology in system evaluation, a low TRL technology's high potential is counterbalanced by its inherent high risk and high uncertainty. As a result, the assessment of the potential impact of low TRL technologies on a new system is exceedingly difficult. In this thesis, a modified Technology Impact Forecasting (TIF) methodology has been proposed that incorporates the novel use of possibility distributions to more accurately quantify the potential of a low TRL technology on a baseline system.

Acute lung injury (ALI) resulting from remote 'indirect' causes is a major problem in sepsis and systemic inflammatory response syndrome (SIRS) but the underlying mechanisms are poorly understood. Circulating microvesicles (MVs) have been implicated as long-range mediators of vascular inflammation and their role as biomarkers in sepsis and SIRS has been widely investigated in clinical studies in recent years. However, the in vivo functional roles of MVs in sepsis and ALI have received less attention. Specifically, the role of in vivo MVs in the development of sepsis/SIRS-induced indirect ALI has not been previously evaluated. We hypothesised that circulating microvesicles (MVs) play a crucial role in propagating inflammation to the lungs, contributing to the development of pulmonary vascular inflammation in indirect ALI. The overall aims of this project were to: 1) evaluate MV uptake by pulmonary vascular cells and the mechanisms involved, 2) characterise the intravascular production of MVs in animal models of sepsis and sterile extrapulmonary organ injury, and 3) identify the contribution of in vivo-derived circulating MVs to the development of indirect ALI. The major findings of this work were that during sub-clinical endotoxaemia in mice, lung-marginated Ly6Chigh monocytes become a major target for circulating MV uptake via a phosphatidylserine receptor mechanism1. In mouse models of sepsis and extrapulmonary organ injury, neutrophil- and monocyte-derived MVs were the predominant MV subtypes being produced during endotoxaemia, while platelet- and endothelial-derived MVs were predominant during kidney ischaemia reperfusion injury. When MVs obtained from plasmas of endotoxaemic mice were adoptively transferred to isolated perfused lungs (IPLs), they induced significant increases in lung oedema. Depletion of intravascular lung monocytes by treatment with clodronate liposomes resulted in the reversal of the oedema, demonstrating the role of monocytes in MV-induced ALI. To investigate the contribution of different circulating MV subtypes, we immunoaffinity isolated myeloid (CD11b+) and platelet (CD41+) MVs from endotoxaemic mouse plasmas and transferred these to the IPL. We found that myeloid-MVs induced significant lung oedema and potent release of soluble mediators, whereas platelet-MVs produced a statistically significant, but much lower level of oedema and negligible release of soluble mediators. In summary, these findings indicate an important role of myeloid-derived MVs, particularly those derived from neutrophils and/or monocytes, and their interaction with lung-marginated monocytes in the pathogenesis of pulmonary vascular inflammation in indirect ALI. Further work to elucidate the specific MV molecular effectors mechanism involved will facilitate an enhanced understanding of ALI pathobiology.

The rising popularity of online learning and the global pandemic COVID-19 sped up the use of synchronous online teaching modality in HEIs worldwide. But unsatisfactory learning experiences and isolation were prominent and commonly perceived by learners. The study aimed to examine students' sense of belonging in a synchronous online learning environment, explore underlying factors and their interplay, and provide practical suggestions to online program designers and instructors. This study employed an explanatory sequential mixed-method design to answer the research questions. The findings indicated the students engaged in synchronous online learning amid the pandemic did not suffer from severe isolation but insufficient support from empathetic instructors. Instructor, peer, and learning climate and their subordinate factors were the determinants impacting learners' SOB in the learning setting. Based on the combined findings, the study proposed suggestions to improve learners' SOB in synchronous online learning, including setting up a favorable learning climate, establishing common values in the community, stimulating identified regulation and intrinsic motivation of learners, and leveraging technology to improve interaction with learners. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Mental health stigma is a ubiquitous concern impacting help-seeking in the United States and worldwide, including in college students. Insufficient attention has been given to the cultural context of stigma and help-seeking in Asian Americans, constructs in which culture has inherent relevance. The current study was the first to develop and test the acceptability of an online culturally adapted, values-based stigma and help-seeking intervention for Asian American college students, intentionally framing the benefits of therapy and mental wellness as congruent with values-based behaviors, intending to reduce the social costs and stigma of impaired functioning. A sample of 115 East, South, and Southeast Asian American college students across the U.S. read and listened to narrated stories of college students experiencing mental health symptoms, stigma concerns, and examples of the congruence of benefits from therapy and mental wellness with values. In a repeated measures design counterbalanced for order, these stories included a culturally adapted condition framed with Asian American values and a generic Eurocentric condition framed with European American values. Participants provided quantitative feedback on each condition, as well as specific messages, and completed questionnaires to assess for potential correlates of message acceptability. Notably, all messages regardless of condition were rated highly acceptable (e.g., averages above "equally agree and disagree"), but ratings between conditions were not significantly different. Correlates and subgroups for differential message acceptability are discussed. Future research is needed to further explore the usefulness of discussing values-based behaviors in help-seeking promotion, effective strategies for cultural adaptations, and potential differences for specific populations. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

This thesis examines how different types of human-dog relationship are constructed and how they interplay dynamically in Yulin, where the widely criticised dog-meat festival is held each year. Through an 11-month period of multispecies ethnographic fieldwork, I found that dogs were used for guarding, hunting, fighting, companionship, and food. The first three types of relationship are part of traditional rural life, while the practice of keeping companion dogs as pets is a Western-oriented urban practice, developed through cultural globalisation. The rural relationships are in decline, while the latter two are expanding with urbanisation. Dog-meat eating, originally an occasional rural practice, has transformed into an urban business form, with an economic chain. Broader social processes are fused into the ways that people from different social backgrounds 'do gender'; these include the various types of relationship people construct with dogs. Dogs with good working performance are constructed with rural masculinities identified by rural men, while dogs kept as pets are perceived as cute, constructing femininities for urban young women. Meanwhile, human-dog power dynamics vary with gender, as rural men's affection for working dogs serves their dominance over dogs, while urban woman's affection results in an ethics of care for dogs, counterbalancing this compensated power. Under this compensated power relationship, many women refrain from eating dog meat. However, their voices are marginalised by local men's strong defence of dog meat, which is believed to strengthen men's health. Amidst controversy about the festival, a discourse that categorises dogs into 'pet dogs' and 'Tugo' has become widespread in Yulin. 'Tugou' is the indigenous type of dog used traditionally for guarding, hunting, fighting, and as food. They are generally much less valued than pet dogs. These different social constructions of dogs result in 'dog racism' in Yulin.

The aim of this thesis is to study the flexibility of electricity-intensive industrial processes to adapt their electricity consumption to the available power. Electricity-intensive processes may use hundreds of megawatts during normal operation. An industrial site typically generates electricity locally and distributes it to electrical loads comprising the processes and other equipment. However, if an electrical contingency occurs, the available power reduces and the power consumed by the electrical loads must also reduce. Currently, a process power management system handles an electrical contingency by disconnecting loads until the total consumption of the site is lower than the remaining available power. This operation is named load shedding. If the shed equipment was essential for the process, then the whole process shuts down. The contribution of the thesis is to demonstrate that flexible process operation gives an alternative to load shedding. The concept is to reduce the power available to the process, so that the process can continue to operate but at a lower production rate. An electrical power outage occurs over a time scale of the order of 100ms. Therefore, in flexible operation, the power available to the process also reduces within 100ms. At the same time, the process control system must receive new set points so that the process moves to an operating point that is consistent with the available power. The thesis studied flexible operation of liquefaction of natural gas and aluminium smelting to find the set points for the process controllers as a function of available electrical power. Results show that the reduction in production rate can be ameliorated by adjusting other secondary process variables. The results also show that a process with significant energy storage such as aluminium smelting can continue operating for short periods of power reduction even with a very significant loss of available power. The final chapters of the thesis discuss how to generalize the study of flexible operation so that it can also be applied to other electricity-intensive processes.

Eddy diffusion is commonly used to characterise subgrid-scale mixing of tracer quantities in geophysical fluid simulations. Limited by data availability, estimating eddy diffusivity from observational data remains challenging. This thesis describes a novel Bayesian framework to infer ocean transports and diffusivity fields from Lagrangian trajectories data. Modelling the Lagrangian trajectories by a stochastic differential equation whose transition density is given by the advection--diffusion equation, this framework produces a posterior probability distribution for the parameters defining the transport and diffusivity fields, enabling uncertainty quantification. In this thesis, Lagrangian trajectories from a three-layer quasigeostrophic double-gyre configuration are used to test the inference schemes. The double-gyre is a classic idealisation of large-scale ocean circulation. Mesoscale eddies are continuously produced and dissipated, leading to a complicated time-dependent flow which can plausibly be coarse-grained as diffusion and suitably used to validate the new inference schemes. Different approaches are implemented based on the Bayesian framework. In a local approach, the ocean domain is divided into an array of cells. Cell-wise defined linear velocity and constant diffusivity fields are inferred using the displacement data of Lagrangian particles originating from the cell. This approach proves capable of estimating the diffusivity in areas with a slow flow such that particles remain in the neighbourhood of their originating cell, but it fails to account for the particle trajectories straddling multiple cells in the considered time interval. An approach to correct the inference for particles straddling two cells is devised using large deviation theory, assuming the dominance of advective transport over diffusive transport. This approach successfully infers piecewise constant velocity and diffusivity using synthesised trajectories, especially in the limit of increasing dominance of advection. A global approach is then developed to infer velocity and diffusivity fields defined on the entire domain. This resolves the locality restriction on the trajectory data in the local approach. A naïve implementation of the global inference, however, involves an exceedingly large number of solutions to the advection--diffusion equation. A data coarse-graining approach is applied to overcome the computational challenge. The impact of the data coarse-graining procedures is quantified in the limit of large data. The global approach is applied to the double-gyre simulation data, using a finite volume method for the solution of advection-diffusion equation. The results demonstrate that the global approach enables a robust inference of the mean flow and diffusivity fields at varying sampling intervals.

The metacognitive model of psychological disorders, also known as the self-regulatory executive function model (S-REF; Wells and Matthews, 1994, 1996), suggests that dysfunctional metacognitions are important vulnerability factors that underlie psychological disorders. Specifically, that metacognitive thought control strategies and metacognitive beliefs are positively associated with psychological disorder symptoms. Whilst their contribution to disorder has been established in adults, less is known about these relationships in the younger population. Furthermore, few studies have explored the early life factors that might influence dysfunctional metacognitive beliefs. As such, the thesis explored the relationship between metacognitive control strategies and symptoms in children and adolescents and the early life factors (e.g. household environment, traumatic events, parenting) that may contribute to dysfunctional metacognitive beliefs. Paper 1 is a systematic review of the literature on the association between thought control and psychopathological symptoms amongst children and adolescents. The review highlights that elevated use of thought control strategies is positively associated with symptoms of anxiety and post-traumatic stress. Furthermore, individual differences in specific thought control strategies such as worry and punishment showed the most consistent relationships with symptoms of anxiety, trauma and depression. The results support the applicability of the metacognitive model in younger populations. Paper 2 evaluated if early exposure to adverse environments, traumatic events, and abusive relationships with caregivers were associated with elevated maladaptive metacognitive beliefs. The study found that higher dysfunctional metacognitive beliefs were associated with a lower current age, lower educational status, greater perceived early setbacks and lower perceived success in childhood. Disadvantaged household environments alone did not contribute to dysfunctional metacognitions and relationships with parenting factors were unreliable. Early emotional abuse was the only factor that showed a consistent positive contribution across dysfunctional metacognitions. The results suggest that possible adverse effects of emotional abuse should be recognised in the context of metacognitions and may inform elements of parenting interventions. In addition, perceptions of personal success and parenting factors may be worthwhile areas for future metacognition research. Paper 3 is a critical appraisal of Papers 1 and 2 and offers a wider discussion of the challenges faced in conducting research in this area and the lessons learned about the research process. In summary, this thesis has highlighted that early emotional abuse is an important correlate of metacognitive beliefs and elevated thought control, specifically that characterised by worry and punishment is positively associated with a range of psychopathological symptoms amongst children and adolescents. Both studies provide evidence that support the applicability of the metacognitive model of psychological disorder in children and adolescents.

In this thesis, we focus on the analysis of a new generation of explicit numerical algorithms for (non-linear) random systems and their applications in computational statistics, non-convex optimization, data science, and finance. In the first part, a tamed (explicit) order 1.5 algorithm is proposed to approximate solutions of stochastic differential equations (SDEs) with super-linear coefficients. Under certain conditions on the coefficients, a convergence result in L 2 is obtained. Then, in the second part, a new higher order Langevin Monte Carlo (LMC) algorithm is constructed, which is based on the application of an order 1.5 scheme to the Langevin SDE. The proposed LMC algorithm is considered in the context of sampling from a target distribution π that has a density πˆ on R d known up to a normalizing constant. To obtain the convergence results, − log ˆπ is assumed to have a locally Lipschitz gradient and its third derivative is locally Hölder continuous with exponent α ∈ (0, 1]. Non-asymptotic bounds are established for the convergence to stationarity of the new sampling method with convergence rate 1 + α/2 in Wasserstein distance, while it is shown that the rate is 1 in total variation even in the absence of convexity. In particular, in the case where − log ˆπ is strongly convex and its gradient is Lipschitz continuous, explicit constants are provided. Finally, in the last part of the thesis, the stochastic gradient Langevin dynamics (SGLD) algorithm is considered, which can be viewed as an extension of the unadjusted Langevin algorithm (ULA). We focus on a stochastic optimization problem via the SGLD algorithm. Crucially, the aim is to obtain non-asymptotic error bounds of the SGLD algorithm with discontinuous gradient H(θ, x). Theoretical guarantees in Wasserstein distances are provided under such an assumption for both convex and non-convex objective functions. Moreover, explicit upper estimates are obtained for the expected excess risk associated with the approximation of global minimizers of these objective functions. Numerical results for key examples in statistics and finance are presented which support the main findings.

This thesis explores the BBC programme, Question Time, treating it as an instantiation of Audience Participation Political Debate (APPD). It examines the nature of political conversation with a focus on the relationship between the practices of overlap and intersubjectivity. This study also addresses the question of why overlap occurs frequently during the course of the conversation in Question Time and how it contributes to the construction, restoration and maintenance of intersubjectivity. The data consists of 16-hours of recordings of Question Time that were aired between January and June 2016. This study uses Conversation Analysis to uncover and examine the sequence organization of overlapping talk in terms of overlapping questions, overlapping statements and overlapping applause. The findings demonstrate that in this APPD context overlapping questions function to solicit the breakdown of intersubjectivity and project the next turns to do repairs. In contrast, overlapping statements and applause serve as an indication of agreement and disagreement among participants, which are found to be the sites on which intersubjectivity rests. The findings of this study contribute to a better understanding of APPD and how in this genre of hybrid media formats the practice of overlap functions. This media format provides an arena that allows the participants greater opportunities to defend and repair their political stances, as well as to display agreements and negotiate disagreements. In addition, the findings add new knowledge to our understanding of the architecture of intersubjectivity in APPD that intersubjectivity can be constructed via the mechanism of negotiation and restored and maintained via repair mechanism.

Ongoing language shift to Taiwanese Mandarin is a pressing concern in Taiwan. With the concerns of losing the rich linguistic and cultural assets of Taiwan's multilingual society, this study sets out to explore the language maintenance endeavours in primary schools, focusing on Daighi. Exploration of language attitudes is the angle this study adopts to approach language shift, looking specifically at whether language attitudes are promoted through the mandatory local languages class at primary school level. However, a large piece of the picture would be missed without the evaluation of the context, which is crucial to understand Daighi's position. Sociocultural theory is then adopted as an analytical lens to view teachers' practices as mediated actions, and to make visible the impact of context in Daighi maintenance. Interviews are used to explore the insights of the frontline Daighi teachers, and Daighi classes of these teachers are observed to investigate their practices, and to match these with their perceptions. In spite of the good teaching practices found at schools and attitudes to support language maintenance, there is still a gap in terms of actual language maintenance, which is defined as developing students to become functional bilinguals (Li Wei, 2006). It is possible that language maintenance is not best achieved by focusing on classroom practice alone. The Discussion Chapter then presents the mediators from global level, national level to classroom, students and teacher agency. Language policy, educational system, and perceived language attitudes of the government, local authority, school, colleagues, family and students emerge as influential mediators that contribute to the ongoing language shift to Taiwanese Mandarin. This study provides an analytical insight into Taiwanese local language education and language attitudes. Through engaging with the teachers, it also inspired critical reflections of their own practices. The findings of this study demonstrate an in-depth understanding of Daighi maintenance and shift, and provide a starting point for further research in Daighi, and in the area of language maintenance in multilingual settings.