7,728 research outputs found

    Undergraduate Catalog of Studies, 2023-2024

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    Coordinating virus research: The Virus Infectious Disease Ontology

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    The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of fundamental concern. Ontologies––structured, controlled, vocabularies––are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the COVID-19 research domain, by following principles of the Open Biological and Biomedical Ontology (OBO) Foundry and by reusing existing ontologies such as the Infectious Disease Ontology (IDO) Core, which provides terminological content common to investigations of all infectious diseases. We report here on the development of an IDO extension, the Virus Infectious Disease Ontology (VIDO), a reference ontology covering viral infectious diseases. We motivate term and definition choices, showcase reuse of terms from existing OBO ontologies, illustrate how ontological decisions were motivated by relevant life science research, and connect VIDO to the Coronavirus Infectious Disease Ontology (CIDO). We next use terms from these ontologies to annotate selections from life science research on SARS-CoV-2, highlighting how ontologies employing a common upper-level vocabulary may be seamlessly interwoven. Finally, we outline future work, including bacteria and fungus infectious disease reference ontologies currently under development, then cite uses of VIDO and CIDO in host-pathogen data analytics, electronic health record annotation, and ontology conflict-resolution projects

    Graduate Catalog of Studies, 2023-2024

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    Investigating the impact of lung cancer cell-of-origin on tumour metabolic phenotype and heterogeneity

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    Non-small-cell lung cancer has been described as highly heterogenous which results in different metabolic phenotypes. There are multiple factors which contribute to this heterogeneity, one of which is the tumour cell-of-origin. In the lung, there are five cell types reported to be cells-of-origin: alveolar epithelial type 2, club, basal, neuroendocrine and bronchioalveolar stem cells. This project focuses on the interaction between the cell-of-origin and the metabolic phenotype of lung cancer, and we aim to assess the contribution of the cell-of-origin to lung cancer metabolic resultant phenotype and heterogeneity. To accomplish this, we have established two complementary model systems, one in vitro and one in vivo. In our in vitro model, we isolated specific lung cell types, including AT2 cells, basal cells, and club cells, utilising their unique cell surface markers. By introducing oncogenic KRAS mutations and deleting the P53 gene, we are creating lineage-restricted organoids. These organoids will serve as valuable tools for characterizing the metabolic aspects of tumours arising from different cell-of-origin backgrounds within an in vitro setting. In our in vivo model, we induced NSCLC tumours in mice with genetic modifications using viral vectors, namely Ad5-mSPC-Cre, Ad5-CC10-Cre, and Ad5- bk5-Cre. These vectors are selectively expressed in AT2, club, and basal cells, respectively. To ensure the validity of our comparisons, we have carefully monitored tumour growth dynamics and burden in these mouse models. Our comprehensive analysis has revealed three distinct transcriptomic subtypes (S1, S2, and Acetate) within these NSCLC tumours. Notably, S1 and Acetate subtypes are enriched in tumours originating from specific cell types. Positron emission tomography (PET) imaging has unveiled metabolic variations, with S1 tumours displaying heightened [18F]FDG uptake and the Acetate subtype exhibiting increased [11C]acetate uptake. Furthermore, our multi-omics approach, encompassing transcriptomics, proteomics, and metabolomics, has exposed disparities in critical metabolic pathways, such as glycolysis, hypoxia response, and apoptosis. In summary, our research provides a comprehensive examination of the metabolic heterogeneity of NSCLC based on the cell-of-origin independently of genomic alterations

    Leveraging social media, big data, and smart technologies for intercultural communication and effective leadership: Empirical study at the Ministry of Digital Economy and Entrepreneurship

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    The objective of this study was to evaluate the impact of social media, big data, and smart technology on intercultural communication and effective leadership inside the Ministry of digital & entrepreneurship. The main objective was to investigate the influence of these technical elements on organizational behavior and the efficacy of leadership within the particular setting of a government ministry dedicated to digital economy and entrepreneurship. In order to accomplish this goal, a thorough empirical inquiry was done, which included gathering data from important individuals involved in the Ministry. The study intentionally selected a sample size of 379 individuals, who represented various responsibilities within the Ministry. The process of data gathering entailed the distribution of surveys and the conduction of interviews to acquire valuable insights and viewpoints from the participants. The utilization of this approach yielded a resilient dataset that is well-suited for thorough investigation. The study explored the complex connection between the use of social media platforms, the implementation of big data analytics, and the incorporation of smart technologies in influencing the dynamics of intercultural communication and leadership inside the Ministry. The results emphasized the substantial influence of social media in promoting intercultural communication and cooperation among personnel within the Ministry. Moreover, the implementation of big data analytics has become a crucial element in improving decision-making processes, impacting several facets of leadership efficacy, strategic planning, and employee involvement. Smart technologies were recognized as crucial elements in establishing efficient communication channels and facilitating effective leadership practices. The study's findings emphasized the beneficial impacts of utilizing social media, big data, and smart technology in the Ministry of digital & entrepreneurship. The research highlighted the significance of government organizations incorporating these technologies in a proactive manner to foster a work environment characterized by improved multicultural communication, well-informed decision-making and efficient leadership. This study makes a substantial contribution to the comprehension of how technological improvements might influence organizational behavior and leadership practices in a government setting. It provides essential insights for policymakers, leaders, and researchers. The findings have broader significance beyond the Ministry, serving as a basis for additional investigation into the use of technology in intercultural communication and leadership effectiveness inside government institutions

    The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

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    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

    Dataflow Programming and Acceleration of Computationally-Intensive Algorithms

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    The volume of unstructured textual information continues to grow due to recent technological advancements. This resulted in an exponential growth of information generated in various formats, including blogs, posts, social networking, and enterprise documents. Numerous Enterprise Architecture (EA) documents are also created daily, such as reports, contracts, agreements, frameworks, architecture requirements, designs, and operational guides. The processing and computation of this massive amount of unstructured information necessitate substantial computing capabilities and the implementation of new techniques. It is critical to manage this unstructured information through a centralized knowledge management platform. Knowledge management is the process of managing information within an organization. This involves creating, collecting, organizing, and storing information in a way that makes it easily accessible and usable. The research involved the development textual knowledge management system, and two use cases were considered for extracting textual knowledge from documents. The first case study focused on the safety-critical documents of a railway enterprise. Safety is of paramount importance in the railway industry. There are several EA documents including manuals, operational procedures, and technical guidelines that contain critical information. Digitalization of these documents is essential for analysing vast amounts of textual knowledge that exist in these documents to improve the safety and security of railway operations. A case study was conducted between the University of Huddersfield and the Railway Safety Standard Board (RSSB) to analyse EA safety documents using Natural language processing (NLP). A graphical user interface was developed that includes various document processing features such as semantic search, document mapping, text summarization, and visualization of key trends. For the second case study, open-source data was utilized, and textual knowledge was extracted. Several features were also developed, including kernel distribution, analysis offkey trends, and sentiment analysis of words (such as unique, positive, and negative) within the documents. Additionally, a heterogeneous framework was designed using CPU/GPU and FPGAs to analyse the computational performance of document mapping

    It doesn't end with closure:Optimizing health care throughout life after esophageal atresia repair

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    Elucidating How MLH1 Loss Regulates a Metabolic Phenotype in Endometrial Cancer

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    Endometrial cancer is the fourth most common cancer in women and the most common gynaecological malignancy in the developed world. No new systemic treatments for endometrial cancer have been developed in recent years and its incidence is expected to double over the next decade. As such, there is a need to better understand key molecular pathways that are altered in the disease and could be targeted by novel treatments. The DNA MMR pathway is lost in approximately 30% of endometrial cancers. A small proportion of these are caused by germline mutations in one of the four MMR genes, however, the majority result from the epigenetic silencing of MLH1. Recently, our lab has shown that MLH1-deficient cells demonstrate a mitochondrial phenotype characterised by reduced OXPHOS, reduced mtDNA copy number and Complex I inhibition. OXPHOS-deficient cells must adapt their metabolism to compensate for energy defects and the inability to efficiently use the tricarboxylic acid cycle to generate energy. We hypothesise that this altered metabolism is driving tumourigenesis by increasing the tumour cells' metastatic potential. In this PhD we aimed to further investigate the influence MLH1 loss has on cellular metabolism using MLH1 positive and negative paired endometrial cell lines. Ultimately, we aim to understand whether altered metabolism in MLH1-deficient endometrial cancer may be therapeutically targeted

    It doesn't end with closure:Optimizing health care throughout life after esophageal atresia repair

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