Search results for: Harrison Lik Nang Lau

Authors: Joseph Lillington, Tom Gout, Mike Harrison, Ian Farnan

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The vitrification of high-level nuclear waste within borosilicate glass and its incorporation within a multi-barrier repository deep underground is widely accepted as the preferred disposal method. However, for this to happen, any safety case will require validation that the initially localized radionuclides will not be considerably released into the near/far-field. Therefore, accurate mechanistic models are necessary to predict glass dissolution, and these should be robust to a variety of incorporated waste species and leaching test conditions, particularly given substantial variations across international waste-streams. Here, machine learning is used to predict glass material properties (viscosity, density) and glass leaching model parameters from large-scale industrial data. A variety of different machine learning algorithms have been compared to assess performance. Density was predicted solely from composition, whereas viscosity additionally considered temperature. To predict suitable glass leaching model parameters, a large simulated dataset was created by coupling MATLAB and the chemical reactive-transport code HYTEC, considering the state-of-the-art GRAAL model (glass reactivity in allowance of the alteration layer). The trained models were then subsequently applied to the large-scale industrial, experimental data to identify potentially appropriate model parameters. Results indicate that ensemble methods can accurately predict viscosity as a function of temperature and composition across all three industrial datasets. Glass density prediction shows reliable learning performance with predictions primarily being within the experimental uncertainty of the test data. Furthermore, machine learning can predict glass dissolution model parameters behavior, demonstrating potential value in GRAAL model development and in assessing suitable model parameters for large-scale industrial glass dissolution data.

Keywords: machine learning, predictive modelling, pattern recognition, radioactive waste glass

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Authors: Riaz Ahmed Mangrio

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Reduplication in Urdu-Hindi affects all major word categories, particles, and even nonsensical words. It conveys a variety of meanings, including distribution, emphasis, iteration, adjectival and adverbial. This study will primarily discuss reduplicative structures of nonsensical words in Urdu-Hindi and then briefly look at some examples from other Indo-Aryan languages to introduce the debate regarding the same structures in them. The goal of this study is to present counter-evidence against Keane (2005: 241), who claims “the base in the cases of lexical and phrasal echo reduplication is always independently meaningful”. However, Urdu-Hindi reduplication derives meaningful compounds from nonsensical words e.g. gũ mgũ (A) ‘silent and confused’ and d̪əb d̪əb-a (N) ‘one’s fear over others’. This needs a comprehensive examination to see whether and how the various structures form patterns of a base-reduplicant relationship or, rather, they are merely sub lexical items joining together to form a word pattern of any grammatical category in content words. Another interesting theoretical question arises within the Optimality framework: in an OT analysis, is it necessary to identify one of the two constituents as the base and the other as reduplicant? Or is it best to consider this a pattern, but then how does this fit in with an OT analysis? This may be an even more interesting theoretical question. Looking for the solution to such questions can serve to make an important contribution. In the case at hand, each of the two constituents is an independent nonsensical word, but their echo reduplication is nonetheless meaningful. This casts significant doubt upon Keane’s (2005: 241) observation of some examples from Hindi and Tamil reduplication that “the base in cases of lexical and phrasal echo reduplication is always independently meaningful”. The debate on the point becomes further interesting when the triplication of nonsensical words in Urdu-Hindi e.g. aẽ baẽ ʃaẽ (N) ‘useless talk’ is also seen, which is equally important to discuss. The example is challenging to Harrison’s (1973) claim that only the monosyllabic verbs in their progressive forms reduplicate twice to result in triplication, which is not the case with the example presented. The study will consist of a thorough descriptive analysis of the data for the purpose of documentation, and then there will be OT analysis.

Keywords: reduplication, urdu-hindi, nonsensical, optimality theory

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Authors: Lamphong Volady

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The primary purpose of this study was to explore the traditional cuisine (local food) of Luangprabang Province in line with the Lao PDR’s One District One Product Policy. Another purpose of the study was to examine channels used to present local food, reasons to preserve and promote local food, as well as local food preservation and promotion strategies. It also aimed at testing correlation hypotheses whether there is a statistically significant relationship between enjoyment of having local food and willingness to promote local cuisines becoming international cuisines, attractiveness to consume local food, preservation and promotion of local food problems, and local people’s occupations. The Convergent Parallel Mixed Methods were employed in this study. The results of the study showed that several local cuisines were found to be local food of Luangprabang Province, namely Jeow Bon (Chilli dipping suace), Or Lam or aw lahm (stew buffalo skin, herbs, Mai sakaan), Kai Pan (River Weed Dry), Tam Mak Houng Luangprabang (Papaya Salad), Nang (Yam Buffalo Skin Dry), Sai Oor (Sausage), Laap Sin Koay Sai Mar-Keua Pao (Beef Salad with Roasted Eggplants), Orm Born (Taro leaves Stew), Oor Nor Mai (Bamboo Shoot Sausage), Jeow Nam Poo (Pickled Crab Chillies), Mok Dok Kae (steaming or roasting a Dok Kae Wrapp), Nor Sa Wan, Kao Noom Kee Noo, Kao Noom Ba Bin. It also depicted that YouTube, Facebook, and TikTok were multiple social channels or platforms which were found to be used to introduce traditional food as well as television, smartphone, word of mouth, Lao food fairs and other provincial events. The study also found that local food should be preserved and promoted since traditional food is not only ancestral, ancient, traditional, and local cuisines, but it is also wisdom, unique, and national cuisine. The study also found that people feel attracted to consuming local food because local food is delicious, unique, clean, nutritious, non-contaminated and natural. The study showed that lack of funds to produce local food, inadequate draw materials, lack material to store products, insufficient place to produce and lack of related organizations engagement were found to be problems for preserving and promoting traditional food. Finally, the result of the study revealed that there is a statistically significant weak relationship between enjoyment of having local food and willingness to promote local cuisines becoming international cuisines (R²= 4.5%), (p-value <0.001). There is a statistically significant moderate relationship between enjoyment of having local food and attractiveness to consume local food (R²= 7.8%), (p-value <0.001). However, there is a statistically insignificant relationship between enjoyment of having local food and preservation and promotion of local food problems (R²= 1.8%), (p-value = 0.086). It was found that there is a statistically insignificant relationship between enjoyment of having local food and local people’s occupations (R²= 0.0%), (p-value = 0.929).

Keywords: local food, preservation, promotion, traditional food, cuisines

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Authors: Tran Thi Thuy Oanh, Nguyen Ngoc Bao Tran

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In the view of Cognitive Linguistics (CL), knowledge and experience of things and events are used by human beings in expressing concepts, especially in their daily life. The human conceptual system is considered to be fundamentally metaphorical in nature. It is also said that the way we think, what we experience, and what we do everyday is very much a matter of language. In fact, language is an integral factor of cognition in that CL is a family of broadly compatible theoretical approaches sharing the fundamental assumption. The relationship between language and thought, of course, has been addressed by many scholars. CL, however, strongly emphasizes specific features of this relation. By experiencing, we receive knowledge of lives. The partial things are ideal domains, we make use of all aspects of this domain in metaphorically understanding abstract targets. The paper refered to applying this theory on pragmatics lessons for major English students at University of Foreign Language Studies - The University of Da Nang, Viet Nam. We conducted the study with two third – year students groups studying English pragmatics lessons. To clarify this study, the data from these two classes were collected for analyzing linguistic perspectives in the view of CL and traditional concepts. Descriptive, analytic, synthetic, comparative, and contrastive methods were employed to analyze data from 50 students undergoing English pragmatics lessons. The two groups were taught how to transfer the meanings of expressions in daily life with the view of CL and one group used the traditional view for that. The research indicated that both ways had a significant influence on students' English translating and interpreting abilities. However, the traditional way had little effect on students' understanding, but the CL view had a considerable impact. The study compared CL and traditional teaching approaches to identify benefits and challenges associated with incorporating CL into the curriculum. It seeks to extend CL concepts by analyzing metaphorical expressions in daily conversations, offering insights into how CL can enhance language learning. The findings shed light on the effectiveness of applying CL in teaching and learning English pragmatics. They highlight the advantages of using metaphorical expressions from daily life to facilitate understanding and explore how CL can enhance cognitive processes in language learning in general and teaching English pragmatics to third-year students at the UFLS - UDN, Vietnam in personal. The study contributes to the theoretical understanding of the relationship between language, cognition, and learning. By emphasizing the metaphorical nature of human conceptual systems, it offers insights into how CL can enrich language teaching practices and enhance students' comprehension of abstract concepts.

Keywords: cognitive linguisitcs, lakoff and johnson, pragmatics, UFLS

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Authors: Kan Yu, Khui Hung Lee, Eben Afrifa-Yamoah, Jing Guo, Katrina Harrison, Jack Goldblatt, Nicholas Pachter, Jitian Xiao, Guicheng Brad Zhang

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Background and Significance of the Study: Congenital Heart Defects (CHDs) are the most common malformation at birth and one of the leading causes of infant death. Although the exact etiology remains a significant challenge, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of congenital heart defects. At present, no existing DNA methylation biomarkers are used for early detection of CHDs. The existing CHD diagnostic techniques are time-consuming and costly and can only be used to diagnose CHDs after an infant was born. The present study employed a machine learning technique to analyse genome-wide methylation data in children with and without CHDs with the aim to find methylation biomarkers for CHDs. Methods: The Illumina Human Methylation EPIC BeadChip was used to screen the genome‐wide DNA methylation profiles of 24 infants diagnosed with congenital heart defects and 24 healthy infants without congenital heart defects. Primary pre-processing was conducted by using RnBeads and limma packages. The methylation levels of top 600 genes with the lowest p-value were selected and further investigated by using a random forest approach. ROC curves were used to analyse the sensitivity and specificity of each biomarker in both training and test sample sets. The functionalities of selected genes with high sensitivity and specificity were then assessed in molecular processes. Major Findings of the Study: Three genes (MIR663, FGF3, and FAM64A) were identified from both training and validating data by random forests with an average sensitivity and specificity of 85% and 95%. GO analyses for the top 600 genes showed that these putative differentially methylated genes were primarily associated with regulation of lipid metabolic process, protein-containing complex localization, and Notch signalling pathway. The present findings highlight that aberrant DNA methylation may play a significant role in the pathogenesis of congenital heart defects.

Keywords: biomarker, congenital heart defects, DNA methylation, random forest

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Authors: Jude Harrison

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Child protection is a complex and sensitive practice. The core responsibility is the care and protection of children and young people who have been subject to or who are at risk from abuse and neglect. The work involves investigating allegations of harm, preparing for and making representations to the legal system, and case planning and management across a continuum of complicated care interventions. Professionals’ learning for child protection practice is evident in a range of literature investigating multiple learning processes such as university preparation, student placements, professional supervision, training, and other post-qualifying professional development experiences at work. There is, however, very limited research into how caseworkers learn in and through their daily practice. Little is known, therefore, about how learning at work unfolds for caseworkers, the dimensions in which it can be understood or the ways in which it can be best facilitated and supported. Compounding this, much of the current child protection learning literature reflects an orthodox conception of learning as mentalistic and individualised, in which knowledge is typically understood as abstract theory or as technical skill or competency. This presentation outlines key findings from a PhD research study that explored learning at work for statutory child protection caseworkers from an alternative interpretation of learning using a practice theory approach. Practice theory offers an interpretation of learning as performative and grounded in situated experience. The findings of the study show that casework practice is both a mode and site of learning. The study was ethnographic in design based and followed 17 child protection caseworkers via in-depth interviews, observations and participant reflective journaling. Inductive and abductive analysis was used to organise and interpret the data and expand analysis, leading to themes. Key findings show learning to be a sociomaterial property of doing; the social ontological character of learning; and teleoaffectivity as a feature of learning. The findings contribute to theoretical and practical understandings of learning and practice in child protection, child welfare and the professional learning literature more broadly. The findings have potential to contribute to policy directions at state, territory and national levels to enhance child protection practice and systems.

Keywords: adiult learning, workplace learning, child welfare, sociomaterial, practice theory

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Authors: Humphrey Agevi, Harrison Tsingalia, Richard Onwonga, Shem Kuyah

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Most of the world ecosystems have been affected by the effects of climate change. Efforts have been made to mitigate against climate change effects. While most studies have been done in forest ecosystems and pure plant plantations, trees on farms including agroforestry have only received attention recently. Agroforestry systems and tree cover on agricultural lands make an important contribution to climate change mitigation but are not systematically accounted for in the global carbon budgets. This study sought to: (i) determine tree diversity in different agroforestry practices; (ii) determine tree biomass in different agroforestry practices. Study area was determined according to the Land degradation surveillance framework (LSDF). Two study sites were established. At each of the site, a 5km x 10km block was established on a map using Google maps and satellite images. Way points were then uploaded in a GPS helped locate the blocks on the ground. In each of the blocks, Nine (8) sentinel clusters measuring 1km x 1km were randomized. Randomization was done in a common spreadsheet program and later be downloaded to a Global Positioning System (GPS) so that during surveys the researchers were able to navigate to the sampling points. In each of the sentinel cluster, two farm boundaries were randomly identified for convenience and to avoid bias. This led to 16 farms in Kakamega South and 16 farms in Kakamega North totalling to 32 farms in Kakamega Site. Species diversity was determined using Shannon wiener index. Tree biomass was determined using allometric equation. Two agroforestry practices were found; homegarden and hedgerow. Species diversity ranged from 0.25-2.7 with a mean of 1.8 ± 0.10. Species diversity in homegarden ranged from 1-2.7 with a mean of 1.98± 0.14. Hedgerow species diversity ranged from 0.25-2.52 with a mean of 1.74± 0.11. Total Aboveground Biomass (AGB) determined was 13.96±0.37 Mgha-1. Homegarden with the highest abundance of trees had higher above ground biomass (AGB) compared to hedgerow agroforestry. This study is timely as carbon budgets in the agroforestry can be incorporated in the global carbon budgets and improve the accuracy of national reporting of greenhouse gases.

Keywords: agroforestry, allometric equations, biomass, climate change

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Authors: Gaoyang Meng, Philip Harrison

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When manufacturing composite laminates, the fibre directions within the laminate are never perfectly straight and inevitably contain some degree of stochastic in-plane waviness or ‘meandering’. In this work we aim to understand the relationship between the degree of meandering of the fibre paths, and the resulting uncertainty in the laminate’s final mechanical properties. To do this, a numerical tool is developed to automatically generate meandering fibre paths in each of the laminate's 8 plies (using Matlab) and after mapping this information into finite element simulations (using Abaqus), the statistical variability of the tensile mechanical properties of a [45°/90°/-45°/0°]s carbon/epoxy (IM7/8552) laminate is predicted. The stiffness, first ply failure strength and ultimate failure strength are obtained. Results are generated by inputting the degree of variability in the fibre paths and the laminate is then examined in all directions (from 0° to 359° in increments of 1°). The resulting predictions are output as flower (polar) plots for convenient analysis. The average fibre orientation of each ply in a given laminate is determined by the laminate layup code [45°/90°/-45°/0°]s. However, in each case, the plies contain increasingly large amounts of in-plane waviness (quantified by the standard deviation of the fibre direction in each ply across the laminate. Four different amounts of variability in the fibre direction are tested (2°, 4°, 6° and 8°). Results show that both the average tensile stiffness and the average tensile strength decrease, while the standard deviations increase, with an increasing degree of fibre meander. The variability in stiffness is found to be relatively insensitive to the rotation angle, but the variability in strength is sensitive. Specifically, the uncertainty in laminate strength is relatively low at orientations centred around multiples of 45° rotation angle, and relatively high between these rotation angles. To concisely represent all the information contained in the various polar plots, rotation-angle dependent Weibull distribution equations are fitted to the data. The resulting equations can be used to quickly estimate the size of the errors bars for the different mechanical properties, resulting from the amount of fibre directional variability contained within the laminate. A longer term goal is to use these equations to quickly introduce realistic variability at the component level.

Keywords: advanced composite laminates, FE simulation, in-plane waviness, tensile properties, uncertainty quantification

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Authors: E. V. Fakhrutdinova, K. R. Maksimova, P. B. Chursin

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At the present stage of the society progress the health care is an integral part of both the economic system and social, while in the second case the medicine is a major component of a number of basic and necessary social programs. Since the foundation of the health system are highly qualified health professionals, it is logical proposition that increase of doctor`s professionalism improves the effectiveness of the system as a whole. Professionalism of the doctor is a collection of many components, essential role played by such personal-psychological factors as honesty, willingness and desire to help people, and motivation. A number of researchers consider motivation as an expression of basic human needs that have passed through the “filter” which is a worldview and values learned in the process of socialization by the individual, to commit certain actions designed to achieve the expected result. From this point of view a number of researchers propose the following classification of highly skilled employee’s needs: 1. the need for confirmation the competence (setting goals that meet the professionalism and receipt of positive emotions in their decision), 2. The need for independence (the ability to make their own choices in contentious situations arising in the process carry out specialist functions), 3. The need for ownership (in the case of health care workers, to the profession and accordingly, high in the eyes of the public status of the doctor). Nevertheless, it is important to understand that in a market economy a significant motivator for physicians (both legal and natural persons) is to maximize its own profits. In the case of health professionals duality motivational structure creates an additional contrast, as in the public mind the image of the ideal physician; usually a altruistically minded person thinking is not primarily about their own benefit, and to assist others. In this context, the question of the real motivation of health workers deserves special attention. The survey conducted by the American researcher Harrison Terni for the magazine "Med Tech" in 2010 revealed the opinion of more than 200 medical students starting courses, and the primary motivation in a profession choice is "desire to help people", only 15% said that they want become a doctor, "to earn a lot". From the point of view of most of the classical theories of motivation this trend can be called positive, as intangible incentives are more effective. However, it is likely that over time the opinion of the respondents may change in the direction of mercantile motives. Thus, it is logical to assume that well-designed system of motivation of doctor`s labor should be based on motivational foundations laid during training in higher education.

Keywords: motivation, quality of working life, health system, personal-psychological factors, motivational structure

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Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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Authors: Kevin Baxter, Ron Grove, James Pitney, John Harrison, Ozlem Gumus

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The purpose of this research is to determine the mediating effect of effectiveness of the training provided by Northwestern University’s School of Police Staff and Command (SPSC), on the ability of law enforcement mid-level managers to learn transformational and authentic leadership traits. This study will also evaluate the leadership styles, of course, graduates compared to non-attendees using a static group comparison design. The Louisiana State Police pay approximately $40,000 in salary, tuition, housing, and meals for each state police lieutenant attending the 10-week program of the SPSC. This school lists the development of transformational leaders as an increasing element. Additionally, the SPSC curriculum addresses all four components of authentic leadership - self-awareness, transparency, ethical/moral, and balanced processing. Upon return to law enforcement in roles of mid-level management, there are questions as to whether or not students revert to an “autocratic” leadership style. Insufficient evidence exists to support claims for the effectiveness of management training or leadership development. Though it is widely recognized that transformational styles are beneficial to law enforcement, there is little evidence that suggests police leadership styles are changing. Police organizations continue to hold to a more transactional style (i.e., most senior police leaders remain autocrats). Additionally, research in the application of transformational, transactional, and laissez-faire leadership related to police organizations is minimal. The population of the study is law enforcement mid-level managers from various states within the United States who completed leadership training presented by the SPSC. The sample will be composed of 66 active law enforcement mid-level managers (lieutenants and captains) who have graduated from SPSC and 65 active law enforcement mid-level managers (lieutenants and captains) who have not attended SPSC. Participants will answer demographics questions, Multifactor Leadership Questionnaire, Authentic Leadership Questionnaire, and the Kirkpatrick Hybrid Evaluation Survey. Analysis from descriptive statistics, group comparison, one-way MANCOVA, and the Kirkpatrick Evaluation Model survey will be used to determine training effectiveness in the four levels of reaction, learning, behavior, and results. Independent variables are SPSC graduates (two groups: upper and lower) and no-SPSC attendees, and dependent variables are transformational and authentic leadership scores. SPSC graduates are expected to have higher MLQ scores for transformational leadership traits and higher ALQ scores for authentic leadership traits than SPSC non-attendees. We also expect the graduates to rate the efficacy of SPSC leadership training as high. This study will validate (or invalidate) the benefits, costs, and resources required for leadership development from a nationally recognized police leadership program, and it will also help fill the gap in the literature that exists between law enforcement professional development and transformational and authentic leadership styles.

Keywords: training effectiveness, transformational leadership, authentic leadership, law enforcement mid-level manager

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Authors: Richard Harrison

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Developing competency in mathematics and related critical thinking skills is essential to the education of undergraduate students of Science, Technology, Engineering and Mathematics (STEM). Recently, the HE sector has been impacted by a seemingly widening disconnect between the mathematical competency of incoming first-year STEM students and their entrance qualification tariffs. Despite relatively high grades in A-Level Mathematics, students may initially lack fundamental skills in key areas such as algebraic manipulation and have limited capacity to apply problem solving strategies. Compounded by compensatory measures applied to entrance qualifications during the pandemic, there has been an associated decline in student performance on introductory university mathematics modules. In the UK, a number of online resources have been developed to help scaffold the transition to university mathematics. However, in general, these do not offer a structured learning journey focused on individual developmental needs, nor do they offer an experience coherent with the teaching and learning characteristics of the destination institution. In order to address some of these issues, a bespoke framework has been designed and implemented on our VLE in the Faculty of Engineering & Physical Sciences (FEPS) at the University of Surrey. Called the FEPS Maths Support Framework, it was conceived to scaffold the mathematical development of individuals prior to entering the university and during the early stages of their transition to undergraduate studies. More than 90% of our incoming STEM students voluntarily participate in the process. Students complete a set of initial diagnostic questions in the late summer. Based on their performance and feedback on these questions, they are subsequently guided to self-select specific mathematical topic areas for review using our proprietary resources. This further assists students in preparing for discipline related diagnostic tests. The framework helps to identify students who are mathematically weak and facilitates early intervention to support students according to their specific developmental needs. This paper presents a summary of results from a rich data set captured from the framework over a 3-year period. Quantitative data provides evidence that students have engaged and developed during the process. This is further supported by process evaluation feedback from the students. Ranked performance data associated with seven key mathematical topic areas and eight engineering and science discipline areas reveals interesting patterns which can be used to identify more generic relative capabilities of the discipline area cohorts. In turn, this facilitates evidence based management of the mathematical development of the new cohort, informing any associated adjustments to teaching and learning at a more holistic level. Evidence is presented establishing our framework as an effective early intervention strategy for addressing the sector-wide issue of supporting the mathematical development of STEM students transitioning to HE

Keywords: competency, development, intervention, scaffolding

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Authors: Alexander Harrison Greer, Edward King, Elijah Lee, Safa Obuz, Ruhao Sun, Aditya Sardesai, Toby Ma, Daniel Chow, Bryce Broadus, Calvin Costner, Troy Barnes, Biagio DeSimone, Yeshwin Sankuratri, Yiheng Chen, Holly Golecki

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Although a relatively new field, soft robotics is experiencing a rise in applicability in the secondary school setting through The Soft Robotics Toolkit, shared fabrication resources and a design competition. Exposing students outside of university research groups to this rapidly growing field allows for development of the soft robotics industry in new and imaginative ways. Soft robotic actuators have remained difficult to implement in classrooms because of their relative cost or difficulty of fabrication. Traditionally, a two-part molding system is used; however, this configuration often results in delamination. In an effort to make soft robotics more accessible to young students, we aim to develop a simple, single-mold method of fabricating soft robotic actuators from common household materials. These actuators are made by embedding a soluble polymer insert into silicone. These inserts can be made from hand-cut polystyrene, 3D-printed polyvinyl alcohol (PVA) or acrylonitrile butadiene styrene (ABS), or molded sugar. The insert is then dissolved using an appropriate solvent such as water or acetone, leaving behind a negative form which can be pneumatically actuated. The resulting actuators are seamless, eliminating the instability of adhering multiple layers together. The benefit of this approach is twofold: it simplifies the process of creating a soft robotic actuator, and in turn, increases its effectiveness and durability. To quantify the increased durability of the single-mold actuator, it was tested against the traditional two-part mold. The single-mold actuator could withstand actuation at 20psi for 20 times the duration when compared to the traditional method. The ease of fabrication of these actuators makes them more accessible to hobbyists and students in classrooms. After developing these actuators, they were applied, in collaboration with a ceramics teacher at our school, to a glove used to transfer nuanced hand motions used to throw pottery from an expert artist to a novice. We quantified the improvement in the users’ pottery-making skill when wearing the glove using image analysis software. The seamless actuators proved to be robust in this dynamic environment. Seamless soft robotic actuators created by high school students show the applicability of the Soft Robotics Toolkit for secondary STEM education and outreach. Making students aware of what is possible through projects like this will inspire the next generation of innovators in materials science and robotics.

Keywords: pneumatic actuator fabrication, soft robotic glove, soluble polymers, STEM outreach

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

Abstract:

Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

Abstract:

Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

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Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

Abstract:

Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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