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CD155 density on target cells drives divergent Natural Killer cell responses owing to DNAM-1 loss
No full textActivation of natural killer (NK) cells by transformed targets requires the engagement of activating receptors and commonly a concomitant loss of inhibitory signaling. While the coactivating receptor DNAM-1 is involved in NK cell recognition of tumors expressing the nectin-like molecule CD155, in many cancer types, high expression of CD155 is associated with a poor clinical prognosis. To assess the impact of ligand density on NK cell function, recognition of target cells expressing low and high levels of CD155 was compared. While low levels of CD155 on target cells augmented NK cell activation, most evident in elevated IFN-γ responses, high levels of CD155 drove rapid, activation-induced downregulation of DNAM-1 that did not result in enhanced IFN-γ responses. High levels of CD155 also drove TIGIT loss from the NK cell surface; however, gene editing of TIGIT from primary NK cells had no significant impact on target cell recognition. Although low levels of CD155 induced a degree of DNAM-1 loss, the improved activation was still mediated through DNAM-1, as assessed through selective disruption of the interaction. Similarly, NK cell recognition of targets expressing the nectin CD112, which also engages both DNAM-1 and TIGIT, resulted in modest loss of DNAM-1 expression and heightened IFN-γ responses. Together, these observations suggest that DNAM-1 recognition of its ligands is delicately poised such that low avidity receptor engagement augments NK cell activation, and in particular IFN-γ responses, while stronger engagement can result in the rapid downregulation of DNAM-1 without any significant enhancement of effector responses
Historical investigation into the first burning model of a solid fuel and the origin of the Crank–Nicolson numerical method
No full textCurrent numerical models for the burning of solid fuels have reached a level of complexity that enables researchers to study and predict the intricate thermochemistry involved in various combustion problems, ranging from polymers like PMMA and foams like PU to natural fuels such as timber and vegetation. Yet they share a common mathematical formulation and numerical method that can be traced back to the first solid-burning model, developed for wood combustion during the 1940s. In this paper, we investigate the origins, formulation, and historical context of this model. Developed during the Second World War, it brought together a team of five scientists, Phyllis Nicolson, John Crank, Douglas Hartree, Clement Bamford, and David Malan, from the University of Manchester, the University of Cambridge, and the Special Operations Executive, a British espionage and sabotage organisation. Their task was to solve the governing equations and apply them to improve small incendiary devices for the war effort. The model consists of the heat diffusion equation with a source term representing an Arrhenius-type pyrolysis reaction. The stiffness of the resulting partial differential equation made it difficult to solve with the techniques of the time. This challenge led the team to develop the second-order accurate semi-implicit Crank–Nicolson scheme. This breakthrough not only transformed numerical analysis but also laid the foundations for computational fluid dynamics, modern heat transfer modelling, and advances in combustion and fire science. Overall, we highlight the historical roots of the first solid-fuel burning model, which, though born of wartime combustion research, has had a profound and lasting influence on today’s models and numerical methods
Comparative assessment of retrofit strategies for progressive collapse mitigation in steel-framed structures
No full textA large proportion of the existing building stock has been designed without consideration for progressive collapse and may therefore need retrofitting. To this end, this study compares the performance of three typical retrofit strategies for existing multi-story steel-framed structures subjected to column loss scenarios. The strategies include global measures, such as horizontal bracings placed above the removal zone and a truss system added at the rooftop level, and a local measure based on strengthening the 1st story columns through concrete encasement. Five moment resisting frames, prone to different progressive collapse mechanisms, are considered for case study purposes. Detailed numerical models validated against experimental results are developed to investigate the robustness of the frames before and after retrofitting. Parametric non-linear static analyses are also conducted to optimize the design of the retrofit measures. Additionally, the study assesses the impact of retrofitting on the dynamic response through non-linear dynamic analyses. The results show that the effectiveness of retrofitting depends on several factors, including, most significantly, their ability to redistribute loads, the number of stories, and the type of collapse mechanism (e.g., failure of beams or columns). Moreover, it is shown that global measures have the most favorable influence on the dynamic behavior. The study reveals that no single strategy is effective across all configurations and that case-specific decisions are typically necessary, based on the vulnerabilities in each structure. The paper offers fundamental insights and practical considerations for designing and implementing the various retrofit measures, enabling more holistic and informed selection approaches
Characterizing natural separation and purification during rural polluted water self-purification in the Dashi River: a multidimensional approach to DOM and microbial interactions
No full textThe self-purification capacity of rivers, a natural analog to engineered separation processes, mitigates pollutants through complex physicochemical and biological interactions. This study deciphers these mechanisms along Beijing's Dashi River via a spatial gradient analysis of 15 sites. We integrated size-exclusion chromatography, excitation-emission matrix fluorescence spectroscopy with parallel factor analysis (EEM-PARAFAC), and microbial community profiling to link dissolved organic matter (DOM) transformation with metabolic functions. Downstream self-purification led to a >40 % decrease in terrestrial high molecular weight (HMW) DOM and the reduction of total phosphorus to below the detection limit (0.005 mg L−1). These changes, driven by microbial consortia (e.g., Pseudomonas), simplified DOM structure (evidenced by declining humification index and SUVA₂₅₄) and reduced the formation potential of disinfection by-products by over 60 %. However, a pollution event at Site 13 overwhelmed this capacity, causing a microbial diversity crash (Shannon index decreased by 1.56) and a rebound in turbidity, nutrients, and haloacetic acid yields (76.5 μg L−1). Our findings reveal the synergistic mechanisms of river self-purification and its thresholds, providing fundamental insights for assessing the assimilative capacity and inspiring the development of water purification technologies such as bio-augmented filtration and biofilm-based processes
The plight of prestige: The subjective experiences of women managing chronic physical illnesses and their emotional well-being in the context of the prestige hierarchy
No full textopen access articleChronic illnesses, such as Diabetes and Epilepsy, impact millions globally. Despite the burden of chronic illnesses, a medical hierarchy exists, with many illnesses undervalued in society, hence allocated minimal research funding. This bias disproportionately affects health outcomes for women. This research provides a novel exploration into the lives of women with chronic illnesses of varying levels of prestige, examining commonalities and variations among their illness experience, and the coping strategies they employ to manage their emotional well-being. Six semi-structured interviews were conducted and analysed using Interpretative Phenomenological Analysis. Two superordinate themes were developed: “A fractured reality” and “A restrained reality.” Commonalities across the narrative were manifested in structural inequalities and coping strategies, however, illnesses lower on the prestige hierarchy were evident with an existential conflict with the illness identity. This research demonstrates the structural discrimination of the gender construct and the disparities experienced by women with conditions of lower prestige
British business-government relationships: a case-study of the Burmah Oil Company, 1974-1975
No full textThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.This paper presents a case study of the bailout of the Burmah Oil Company Limited by the British government in 1975, focusing on risk, business-government relations and informality. Analysing negotiations between key governmental and corporate actors at a time of significant economic and political uncertainty, we highlight that while government and business had not developed a structured framework to apply to the economy’s most serious weaknesses, these actors frequently improvised around a theme, in this case, that of risk. We highlight an informal interventionist model within which government was predisposed informally to support businesses in times of crisis. We also highlight that the government dictated the terms of the bailout and imposed risk assessment and monitoring undertaken by private sector accountants. This will illustrate in a novel manner how risk management was deployed in the bailout process, the implications of which had beneficial consequences for the company’s continued existence
Developing Design Guidelines for Educational Robots: Insights from User Research with Preschool Children
No full textChildren aged 4–6 are in a key stage of brain development. During this period, the prefrontal cortex—the part of the brain that controls important skills like paying attention and controlling behaviour—undergoes major changes (Moriguchi & Hiraki, 2020). In China, parents are increasingly focused on their children’s learning during these years, leading to high demand for educational tools like robots. Research shows robots work better than screen-based tools (e.g., tablets) for keeping children engaged and social (Belpaeme et al., 2018). However, many parents and teachers worry about the quality of existing robots, as there are no clear design rules specifically for 4–6- year-olds, even though studies prove children this age learn fastest (Liu et al., 2021).
To address this gap and align with global efforts to improve educational technology (UNESCO, 2019), this study aims to create practical design guidelines for robots that match the unique learning needs of 4–6-year-old children. This study aims to address this gap by creating design guidelines for educational robots targeting children aged four to six in China. The study employs a mixed- methods approach, combining a review of existing literature with direct data collection. Methods include observing 97 children using two types of educational robots in two kindergartens in Shenzhen, China, conducting a questionnaire survey with 114 parents, interviewing 14 kindergarten teachers and three robotics experts, and conducting a focus group with nine parents. These steps ensure a detailed understanding of user needs.
The research outcome is a set of design guidelines that simplify and standardise the development of educational robots for young children. These guidelines help improve product quality, support educational robot designers in creating user-friendly robots for children aged 4-6, By focusing on both practical needs and theoretical foundations, this study contributes to more reliable and effective educational robot products for early childhood development
Unstable Foundations: Class Realignment, Class Formation and Its Political Articulation in an Urban Working-Class Periphery
No full textThis thesis grapples with how contemporary post-Fordist socio-spatial dynamics occurring in urban peripheries are reshaping what is collectively understood by working-class identities, their boundaries and markers, and what limitations social democratic political organisations face when appealing to them. The underlying processes affecting class realignment of the working-class, understood as the reshuffling of partisan loyalties characterising classes at certain periods and places, are addressed through focusing on unpacking the way class formation, meaning the process of shaping the collective class identity, occurs through and across geographic space; and what strategies are deployed by political organisations to articulate resulting class identifications. The need for this research stems from perceived limitations of existing literature when thinking about the role that Space, Class, and Political articulation have. This thesis, therefore, focuses on developing and testing a framework which combines political sociology, political geography, and critical urban studies to study the socio-spatial foundations of class realignment, emphasizing intra-class and intra-place conflicts through space, and applies it to interpret the crisis of social democracy, through a case study of San Jeronimo in Seville (Spain). Located in an urban periphery undergoing socio-spatial changes, hitherto considered a bulwark of social democratic politics, San Jeronimo shows signs of political change. Results indicate that the theoretical framework is successful in shedding light on the underlying transformations in class formation and the limits it puts on political articulation under social democracy. Specifically, intra-class and intra-place conflicts appear as animating a secular crisis of social democratic organisations. Resolving this requires tackling competing class identifications and place-frames existing in urban peripheries. Although focused on processes more relevant to contemporary European urban contexts, the analysis speaks to broader issues relating to the way geography, class and politics interrelate to shape collective understandings of political subjects which are foundational to political dynamics in different historical and geographical settings, bringing Space into political sociology
Examining Perceptions of the Tripartite Relationship in Higher Degree Apprenticeship Programmes
No full textThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The study aims to examine conceptualisations and perceptions of key stakeholders involved in the tripartite relationship of a Higher Degree Apprenticeship (HDA) - apprentice, employer, and higher education institution (HEI) - and how these contribute towards the successful outcomes of a Leadership and Management Senior Leader Degree Apprenticeship (SLA Level 7). The potential of these HDAs to contribute towards progression pathways is essential for integrated learning programmes, as they support strategic business goals and future economic growth.
Group concept mapping (GCM), is used to analyse conceptualisations and perceptions of that relationship. Data were collected using group discussions, analysed using multivariate statistical methods, and debriefed with participants.
HDAs support personal and professional development for senior leadership progression. Three main tensions were identified; the employer-HEI relationship should be contextually matched for work-based learning (WBL), mentors should be trained by the HEI, and soft skill development for demonstrating leadership capability and executive behaviours must be a requirement.
The scope of the study conducted was during a change and update of HDA standards and qualification credit requirements for the SLA.
There is still a need to improve delivery of work-based learning (WBL), addressing practice-theory issues across workplace and academic learning environments.
This article provides an alternative method for examining of the impact of the tripartite relationship on the delivery and outcomes of the SLA
Inclusive Innovation: An Evolving Phenomenon
No full textInclusive Innovation (II) has emerged as a pivotal concept in addressing global inequalities, aiming to engage marginalized communities in innovation processes. Over the last decade, II has evolved and presented itself as a critical mechanism for achieving sustainable and equitable development, particularly in addressing global inequalities, environmental challenges, and the urgency of the United Nations Sustainable Development Goals (SDGs). This entry opens the II discussion by attaining two goals. First, the entry reviews existing literature on the practices that have allowed different players to collaborate codesign and cocreate social and financial values. Five different practice domains are discussed. Then, the entry continues to discuss the barriers and enablers of II across various organizational forms, including social enterprises, business enterprises, multinational corporations (MNCs), nongovernmental organizations (NGOs), and alternative organizations. By taking an inside perspective of these entities, the entry elucidates how organizational structures and strategies influence the implementation of II. It highlights the cross-border implications of II practices and offers contemporary insights for researchers, practitioners, and policymakers