1,765 research outputs found
The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.
Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch\u27s APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch\u27s data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch\u27s analytic tools by developing a customized plugin for OpenAI\u27s ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app
Investigating the Innate Immune Systems of Bats and Their Roles as Zoonotic Viral Reservoirs
The zoonotic spillover of viral pathogens from wild animal reservoirs into human populations remains the leading cause of emerging and re-emerging infectious diseases globally. Bats represent important viral reservoirs, notorious for the diversity and richness of the viruses they host, several of which are highly pathogenic when transmitted to humans. Remarkably, bats appear to host an abundance of these viruses without exhibiting any clinical signs of disease. A dominant hypothesis for this ability suggests that bats can control viral replication early in the innate immune response, which acts as the first line of defence against infection. However, bat immunology remains fundamentally understudied, largely due to their high species diversity and the lack of accessible reagents required for bat research. Therefore, in this work we explored and characterised key components of bat innate immunity to gain a better understanding of bats as viral reservoirs and contribute to the currently limited literature. Here, we demonstrated the in vitro transcriptomic response of the bat model species, Pteropus alecto (P.alecto) upon stimulation with the bat henipavirus Cedar virus and also with a type III bat interferon (paIFNĪ»). These investigations highlighted key transcripts, some of which were immune-related, in the response of bats to the separate stimuli and presents a foundation for further research into significant genes concerned in bat viral infection. Building from genome-wide transcriptomics, three distinctive bat innate immune genes representative of different stages of interferon signalling were selected for comparative genomics and functional characterisation. Our work demonstrated the conservation of genes between bats and humans, including IRF7, IFIT5 and IFI35. Specific findings for IRF7 included its successful translocation to the cell nucleus upon stimulation. IFIT5 and IFI35 were specifically selected for exploration due to previous research demonstrating the respective antiviral and conflicting anti- or pro-viral roles of these genes in humans. Significantly, our research demonstrated the direct antiviral action of P.alecto IFIT5 against negative-sense RNA viruses. Collectively, our findings offer valuable contributions to the field of bat antiviral immunity and provide the framework for future investigative studies into the role and function of the bat innate immune system and bat viral tolerance mechanisms
AI Lifecycle Zero-Touch Orchestration within the Edge-to-Cloud Continuum for Industry 5.0
The advancements in human-centered artificial intelligence (HCAI) systems for Industry 5.0 is a new phase of industrialization that places the worker at the center of the production process and uses new technologies to increase prosperity beyond jobs and growth. HCAI presents new objectives that were unreachable by either humans or machines alone, but this also comes with a new set of challenges. Our proposed method accomplishes this through the knowlEdge architecture, which enables human operators to implement AI solutions using a zero-touch framework. It relies on containerized AI model training and execution, supported by a robust data pipeline and rounded off with human feedback and evaluation interfaces. The result is a platform built from a number of components, spanning all major areas of the AI lifecycle. We outline both the architectural concepts and implementation guidelines and explain how they advance HCAI systems and Industry 5.0. In this article, we address the problems we encountered while implementing the ideas within the edge-to-cloud continuum. Further improvements to our approach may enhance the use of AI in Industry 5.0 and strengthen trust in AI systems
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Understanding the Impact of Covid-19 on Ethnic Minority Students: a Case Study of Open University Level 1 Computing Modules
As reported in [1] āOf the disparities that exist within higher education, the gap between the likelihood of White students and students from Black, Asian or minority ethnic backgrounds getting a first- or upper-second-class degree is among the starkestā. In the Open University (OU) for example, a recent research [2] found students from ethnic minorities to be at least 20% less likely to achieve excellent grades and to spend 4-12% more of study time to achieve the same performance as white students. Moreover, with the advent of COVID-19, a growing body of research suggested that students from these groups of the population, suffer disproportionally from the impacts of the pandemic [3], which inevitably impacts on their study experiences. However, recent research in the OU found that some COVID-19 arrangements such as the change of examination mode and change in work-life patterns have impacted students from ethnic minority backgrounds differently. In this paper we present findings from a project aiming to understand the impact of COVID-19 on ethnic minority studentsā study experiences and performance. By means of a combination of qualitative and quantitative data analytics we first analysed the study performance and the patterns of progression, then by conducting focus groups with the teaching staff we assessed the impact of COVID-19 on the lived experiences of the students.
[1] Black, Asian and Minority Ethnic Student Attainment at UK Universities (2022). Available at: https://www.universitiesuk.ac.uk.
[2] Nguyen Q., Rienties B. Richardson J.T.E. (2020) Learning analytics to uncover inequality in behavioural engagement and academic attainment in a distance learning setting, Assessment & Evaluation in Higher Education, 45:4, 594-606.
[3] Arday, J. and Jones, C. (2022) āSame storm, different boats: The impact of covid-19 on black students and academic staff in UK and US higher education,ā Higher Education. Available at:
https://doi.org/10.1007/s10734-022-00939-0
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Role of Formal and Informal Institutions in Advancing Sustainable Environmental Practices in SMEs of Pakistan's Textile Sector
Economies around the globe have established formal institutions to protect their natural environments (Klewitz et al., 2012, Wahga et al., 2018b), but parallel to them are 'proto-institutions' that also make an important contribution towards sustainable development. A proto-institution, an institution in the making, comprises rules, practices, and technologies that are partially diffused and weakly entrenched but poised to become widely institutionalised (Lawrence et al., 2002, p. 283). This qualitative study examines how proto-institutions in Pakistan's textile sector emerged and played a role in promoting sustainable environmental practices. Stakeholder Theory and Institutional Theory were combined to guide data collection and analysis. Primary data were collected through in-depth interviews, field observations and a field journal, whereas secondary data came from archival records and industry-specific publications. NVIVO 12 was used to sort and prepare data for analysis. Grounded analysis (Gioia et al., 2013, Easterby-Smith et al., 2015) revealed that institutional voids (Mair and Marti, 2009) and institutional gaps (Kolk, 2014) impeded the ability of formal institutions to assist the textile sector and ensure compliance with the established Punjab Environmental Quality Standards (PEQS). Due to these voids and gaps, textile manufacturers and stakeholders collaborated in various ways, resulting in the emergence of proto-institutions. These proto-institutions address the 'knowledge gap' by conducting informative seminars, capacity building workshops, and the production of best practice manuals. They bridge the 'cleaner production gap' by devolving internationally tested cleaner production solutions and assisting with their implementation. In addition, they take steps to close the 'compliance gap' by building the capacity of firms and public institutions. They fill the 'R&D gap' through commercial research into inputs, processes, and product development. They also provide firms with financial assistance through matching grants that help firms overcome their 'financial assistance gap' and acquire international certifications for market entry into global markets and undertake business development services. In doing so, these proto-institutions imposed iii normative and mimetic pressure on firms to adopt green practices while coexisting with formal institutions as compensatory institutions to create environmentally compliant isomorphs (firms). These findings add to the insights about institutional work processes and roles of proto-institutions, by presenting evidence from a previously under-research context: promoting sustainability in a SMEs dominated manufacturing sector of a developing country. In terms of practice, these findings are helpful information for textile manufacturers who are yet unknown to the benefits they could reap by adopting sustainable practices and processes in their manufacturing concerns. The information about collaboration is helpful for stakeholders looking to form new partnerships for responsible production. This study also suggests policymakers to both encourage and collaborate with proto-institutions to accomplish national and international commitments such as SDG 12 - Sustainable Consumption and Production, and race to net zero in textiles. Furthermore, the context specific factors that are affecting the emergence and development of proto-institutions in Pakistanās textile sector could also help policymakers in Pakistan and alike developing countries to overcome institutional gaps and voids in their formal institutional arrangements and better promote sustainable production in their key manufacturing sectors
Re-envisioning access for the digital preservation community: challenges, opportunities and recommendations
Digital material is not new and has been preserved for a couple of decades now. With a growing digital preservation community, and a growing number of practitioners identifying as doing something digital, there is an understanding that this material is here to stay. More and more institutions are publishing digital strategies or creating networks focusing on digital material. However, when looking at this in practice there seems to be a disconnect between what is being stated within these networks and strategies and what is being made accessible to the public.
This thesis will explore this disconnect by first understanding how the digital preservation community has been providing access to this material and how they are envisioning it in the future. This exploration surfaces both a) how digital material can no longer be seen as separate from the infrastructure that ensures its materiality and b) how the provision of access is not just a technological question, but also a social, legal and ethical one.
This thesis will also seek to explore the ways in which those who identify as digital preservation practitioners articulate their role and responsibilities. It will do so by drawing on relevant literature and gaining perspectives from practitioners and other relevant participants through in-depth interviews. Building from this exploration, this thesis will offer recommendations for how this practice can move forward in negotiating the provision of access to digital material in the online public space of the internet.
This research is part of a collaborative project with The National Archives, UK where a number of the ideas encountered during this work were explored in practice. Some of these results have helped shape the recommendations given in the final chapters of this thesis
Handbook Transdisciplinary Learning
What is transdisciplinarity - and what are its methods? How does a living lab work? What is the purpose of citizen science, student-organized teaching and cooperative education? This handbook unpacks key terms and concepts to describe the range of transdisciplinary learning in the context of academic education. Transdisciplinary learning turns out to be a comprehensive innovation process in response to the major global challenges such as climate change, urbanization or migration. A reference work for students, lecturers, scientists, and anyone wanting to understand the profound changes in higher education
The Influence of APOE Genotype on Lipid Droplet Dynamics
Excess lipid droplet (LD) accumulation is associated with several pathological states, including neurodegenerative disorders such as Alzheimerās disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics may contribute to the pathophysiology of AD remains unclear. Apolipoprotein E (ApoE) is a droplet-related protein with a common variant (ApoE4) that confers the largest increase in genetic risk for late-onset AD. Interestingly, ApoE4 is associated with both increased neuroinflammation and excess LD accumulation. This dissertation work seeks to quantitatively profile the lipid and protein composition of LDs between the āneutralā ApoE3 and āriskā ApoE4 isoforms, in order to gain insight into potential LD-driven contributions to AD pathogenesis.
Targeted replacement mice expressing human ApoE3 or ApoE4 were injected with saline (control) or LPS (inflammatory stimulus) and after 24 hours, hepatic lipid droplets were isolated and droplet proteomes and lipidomes were analyzed. Quantitative proteomics showed that LD fractions from E4 mice are enriched for proteins involved in innate immunity, while E3 LDs are enriched for proteins involved in lipid Ć-oxidation. Lipidomics revealed a shift in the distribution of glycerophospholipids in E4 LDs with an increase in multiple phosphatidylcholine (PC) species. There was also substantial overlap between LD proteins and AD-proteomes of human whole brain tissue. To translate these findings to the brain, primary microglia from the same strain of mice were exposed to exogenous lipid, inflammatory stimulation, necroptotic N2A cells (nN2A), or a combination of treatments to evaluate lipid droplet accumulation and impact on cell function. Microglia from ApoE4 mice accumulated more LDs at baseline, with exogenous OA, LPS stimulation, and nN2As as a percentage of E3 control across multiple experiments. E4 microglia also secreted significantly more cytokines (TNF, IL-1Ī², IL-10) than E3 microglia in the control, oleic acid, and nN2A treatment conditions. Interestingly, droplet inhibitors for ACAT and DGAT both decreased droplet accumulation in cells, but did not ameliorate the cytokine response. Finally, we have established a biobank of APOE genotyped peripheral blood mononuclear cells (PBMCs) from research participants. These easily accessible immune cells will serve as a highly translational model to understand LD dynamics as it relates to ApoE and AD risk.
In summary, E4 cells accumulate more LDs compared to E3 under all conditions tested, while the proteomic profile of E4 LDs support the hypothesis that E4 expression increases inflammation under basal conditions. This increased LD formation in non-aged, non-diseased E4 cells may suggest preclinical dysfunction associated with the highest risk APOE genotype, and a better understanding of LD dynamics within these cells and their functional implications may provide novel targets to improve E4-related outcomes
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