2,535 research outputs found

    Recalibrating machine learning for social biases: demonstrating a new methodology through a case study classifying gender biases in archival documentation

    Get PDF
    This thesis proposes a recalibration of Machine Learning for social biases to minimize harms from existing approaches and practices in the field. Prioritizing quality over quantity, accuracy over efficiency, representativeness over convenience, and situated thinking over universal thinking, the thesis demonstrates an alternative approach to creating Machine Learning models. Drawing on GLAM, the Humanities, the Social Sciences, and Design, the thesis focuses on understanding and communicating biases in a specific use case. 11,888 metadata descriptions from the University of Edinburgh Heritage Collections' Archives catalog were manually annotated for gender biases and text classification models were then trained on the resulting dataset of 55,260 annotations. Evaluations of the models' performance demonstrates that annotating gender biases can be automated; however, the subjectivity of bias as a concept complicates the generalizability of any one approach. The contributions are: (1) an interdisciplinary and participatory Bias-Aware Methodology, (2) a Taxonomy of Gendered and Gender Biased Language, (3) data annotated for gender biased language, (4) gender biased text classification models, and (5) a human-centered approach to model evaluation. The contributions have implications for Machine Learning, demonstrating how bias is inherent to all data and models; more specifically for Natural Language Processing, providing an annotation taxonomy, annotated datasets and classification models for analyzing gender biased language at scale; for the Gallery, Library, Archives, and Museum sector, offering guidance to institutions seeking to reconcile with histories of marginalizing communities through their documentation practices; and for historians, who utilize cultural heritage documentation to study and interpret the past. Through a real-world application of the Bias-Aware Methodology in a case study, the thesis illustrates the need to shift away from removing social biases and towards acknowledging them, creating data and models that surface the uncertainty and multiplicity characteristic of human societies

    Converging organoids and extracellular matrix::New insights into liver cancer biology

    Get PDF

    Converging organoids and extracellular matrix::New insights into liver cancer biology

    Get PDF
    Primary liver cancer, consisting primarily of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a heterogeneous malignancy with a dismal prognosis, resulting in the third leading cause of cancer mortality worldwide [1, 2]. It is characterized by unique histological features, late-stage diagnosis, a highly variable mutational landscape, and high levels of heterogeneity in biology and etiology [3-5]. Treatment options are limited, with surgical intervention the main curative option, although not available for the majority of patients which are diagnosed in an advanced stage. Major contributing factors to the complexity and limited treatment options are the interactions between primary tumor cells, non-neoplastic stromal and immune cells, and the extracellular matrix (ECM). ECM dysregulation plays a prominent role in multiple facets of liver cancer, including initiation and progression [6, 7]. HCC often develops in already damaged environments containing large areas of inflammation and fibrosis, while CCA is commonly characterized by significant desmoplasia, extensive formation of connective tissue surrounding the tumor [8, 9]. Thus, to gain a better understanding of liver cancer biology, sophisticated in vitro tumor models need to incorporate comprehensively the various aspects that together dictate liver cancer progression. Therefore, the aim of this thesis is to create in vitro liver cancer models through organoid technology approaches, allowing for novel insights into liver cancer biology and, in turn, providing potential avenues for therapeutic testing. To model primary epithelial liver cancer cells, organoid technology is employed in part I. To study and characterize the role of ECM in liver cancer, decellularization of tumor tissue, adjacent liver tissue, and distant metastatic organs (i.e. lung and lymph node) is described, characterized, and combined with organoid technology to create improved tissue engineered models for liver cancer in part II of this thesis. Chapter 1 provides a brief introduction into the concepts of liver cancer, cellular heterogeneity, decellularization and organoid technology. It also explains the rationale behind the work presented in this thesis. In-depth analysis of organoid technology and contrasting it to different in vitro cell culture systems employed for liver cancer modeling is done in chapter 2. Reliable establishment of liver cancer organoids is crucial for advancing translational applications of organoids, such as personalized medicine. Therefore, as described in chapter 3, a multi-center analysis was performed on establishment of liver cancer organoids. This revealed a global establishment efficiency rate of 28.2% (19.3% for hepatocellular carcinoma organoids (HCCO) and 36% for cholangiocarcinoma organoids (CCAO)). Additionally, potential solutions and future perspectives for increasing establishment are provided. Liver cancer organoids consist of solely primary epithelial tumor cells. To engineer an in vitro tumor model with the possibility of immunotherapy testing, CCAO were combined with immune cells in chapter 4. Co-culture of CCAO with peripheral blood mononuclear cells and/or allogenic T cells revealed an effective anti-tumor immune response, with distinct interpatient heterogeneity. These cytotoxic effects were mediated by cell-cell contact and release of soluble factors, albeit indirect killing through soluble factors was only observed in one organoid line. Thus, this model provided a first step towards developing immunotherapy for CCA on an individual patient level. Personalized medicine success is dependent on an organoids ability to recapitulate patient tissue faithfully. Therefore, in chapter 5 a novel organoid system was created in which branching morphogenesis was induced in cholangiocyte and CCA organoids. Branching cholangiocyte organoids self-organized into tubular structures, with high similarity to primary cholangiocytes, based on single-cell sequencing and functionality. Similarly, branching CCAO obtain a different morphology in vitro more similar to primary tumors. Moreover, these branching CCAO have a higher correlation to the transcriptomic profile of patient-paired tumor tissue and an increased drug resistance to gemcitabine and cisplatin, the standard chemotherapy regimen for CCA patients in the clinic. As discussed, CCAO represent the epithelial compartment of CCA. Proliferation, invasion, and metastasis of epithelial tumor cells is highly influenced by the interaction with their cellular and extracellular environment. The remodeling of various properties of the extracellular matrix (ECM), including stiffness, composition, alignment, and integrity, influences tumor progression. In chapter 6 the alterations of the ECM in solid tumors and the translational impact of our increased understanding of these alterations is discussed. The success of ECM-related cancer therapy development requires an intimate understanding of the malignancy-induced changes to the ECM. This principle was applied to liver cancer in chapter 7, whereby through a integrative molecular and mechanical approach the dysregulation of liver cancer ECM was characterized. An optimized agitation-based decellularization protocol was established for primary liver cancer (HCC and CCA) and paired adjacent tissue (HCC-ADJ and CCA-ADJ). Novel malignancy-related ECM protein signatures were found, which were previously overlooked in liver cancer transcriptomic data. Additionally, the mechanical characteristics were probed, which revealed divergent macro- and micro-scale mechanical properties and a higher alignment of collagen in CCA. This study provided a better understanding of ECM alterations during liver cancer as well as a potential scaffold for culture of organoids. This was applied to CCA in chapter 8 by combining decellularized CCA tumor ECM and tumor-free liver ECM with CCAO to study cell-matrix interactions. Culture of CCAO in tumor ECM resulted in a transcriptome closely resembling in vivo patient tumor tissue, and was accompanied by an increase in chemo resistance. In tumor-free liver ECM, devoid of desmoplasia, CCAO initiated a desmoplastic reaction through increased collagen production. If desmoplasia was already present, distinct ECM proteins were produced by the organoids. These were tumor-related proteins associated with poor patient survival. To extend this method of studying cell-matrix interactions to a metastatic setting, lung and lymph node tissue was decellularized and recellularized with CCAO in chapter 9, as these are common locations of metastasis in CCA. Decellularization resulted in removal of cells while preserving ECM structure and protein composition, linked to tissue-specific functioning hallmarks. Recellularization revealed that lung and lymph node ECM induced different gene expression profiles in the organoids, related to cancer stem cell phenotype, cell-ECM integrin binding, and epithelial-to-mesenchymal transition. Furthermore, the metabolic activity of CCAO in lung and lymph node was significantly influenced by the metastatic location, the original characteristics of the patient tumor, and the donor of the target organ. The previously described in vitro tumor models utilized decellularized scaffolds with native structure. Decellularized ECM can also be used for creation of tissue-specific hydrogels through digestion and gelation procedures. These hydrogels were created from both porcine and human livers in chapter 10. The liver ECM-based hydrogels were used to initiate and culture healthy cholangiocyte organoids, which maintained cholangiocyte marker expression, thus providing an alternative for initiation of organoids in BME. Building upon this, in chapter 11 human liver ECM-based extracts were used in combination with a one-step microfluidic encapsulation method to produce size standardized CCAO. The established system can facilitate the reduction of size variability conventionally seen in organoid culture by providing uniform scaffolding. Encapsulated CCAO retained their stem cell phenotype and were amendable to drug screening, showing the feasibility of scalable production of CCAO for throughput drug screening approaches. Lastly, Chapter 12 provides a global discussion and future outlook on tumor tissue engineering strategies for liver cancer, using organoid technology and decellularization. Combining multiple aspects of liver cancer, both cellular and extracellular, with tissue engineering strategies provides advanced tumor models that can delineate fundamental mechanistic insights as well as provide a platform for drug screening approaches.<br/

    Multimorbidity of cardiometabolic diseases and effectiveness of integrated healthcare system response in sub-Saharan Africa

    Get PDF
    This thesis aims to strengthen the responsiveness of healthcare systems to the management of cardiometabolic multimorbidity in sub-Saharan Africa (SSA). More specifically, four main issues on cardiometabolic multimorbidity in SSA were investigated: the burden of cardiometabolic multimorbidity, chronic care models, the readiness of healthcare facilities to provide integrated care, and the effect of multimorbidity on self-care interventions. A latent class analysis and hierarchical agglomerative cluster analysis in part one show that cardiometabolic diseases occur in distinct clusters of concordant and discordant multimorbidity. These clusters are significant predictors of outpatient visits, hospitalisation, functional disability and quality of life. Multimorbidity is disproportionately highest among persons of high socioeconomic status, women, the middle and old-aged, and those with sedentary lifestyles and obesity. A systematic review and meta-analysis in part two shows that integrated care versus standard care improved systolic blood pressure control in people with multimorbidity. In part three, a national facility assessment survey in Kenya shows that only one in every four healthcare facilities (at all levels) was ready to provide integrated care for cardiovascular diseases and type 2 diabetes. The clinical integration barriers included vertical and unresponsive healthcare services. In part four, a quasi-experimental study of patients with hypertension undergoing a home-based self-care program in Kenya shows that multimorbidity attenuated the effectiveness of patient support groups for hypertension. Overall, the findings of this thesis provide crucial evidence for multimorbidity risk stratification and underscore the importance of tailoring patient-centered care interventions to match the needs of people with cardiometabolic multimorbidity in SSA

    Forschungsbericht / Hochschule Mittweida

    Get PDF

    Inovação na diplomacia cultural: o caso da China

    Get PDF
    This study focuses on the innovation of China’s cultural diplomacy (CCD) by means of the Confucius Institute (CI). The main contents revolve around the following research goals: 1) to understand the strategic framework and practical path of CCD, and to clarify the context of its inheritance and innovation; 2) to analyze whether the CI, epitomized as a crucial innovation of CCD, has improved China’s national image in Portuguese-speaking countries (PSCs) and enhanced the attraction and international competitiveness of Chinese culture; and 3) to explore how China can better formulate its CD strategy in line with the exigencies of the modern era. The study combines the methods of literature review, case study, and questionnaire research to explore the topics from different perspectives to strengthen the scientific nature of the research results. In addition to the introduction and conclusion, the thesis is divided into five chapters. Chapter 1 discusses the connotation and value of CD. Chapter 2 expounds the development and innovation of CCD. Chapter 3 systematically summarizes China’s cultural interaction in its diplomatic process with PSCs. Chapter 4 elaborates on the CI in terms of its operation mode and diplomatic means. Chapter 5 forms the core of the study and involves empirical analysis of case-study and questionnaire data. It aims to investigate the functions, public image, influence, and practical means of CIs in the process of CD. Major findings indicate that CIs in PSCs have achieved ideal social feedback and play a positive role in shaping the image of China. However, according to the different continents where CIs are located, the survey results show distinct characteristics which are closely related to China’s different foreign policies towards Latin America, Europe, and Africa and are determined by the historical experiences and national conditions of the various countries. The future task for CCD is to clarify China’s institutional roots and the cultural genes behind its development by using cultural exchanges and China’s fluid culture to convey a message of China’s pursuit of peace, development, and cooperation.Este estudo tem como foco a inovação da Diplomacia Cultural da China (DCC) através do Instituto Confúcio (IC). Os principais conteúdos giram em torno dos seguintes objetivos de investigação: 1) compreender o enquadramento estratégico e o percurso prático da Diplomacia Cultural da China e clarificar o contexto da sua herança e inovação; 2) analisar se o IC, exemplo de inovação crucial da Diplomacia Cultural da China, melhorou a imagem nacional da China nos Países de Língua Oficial Portuguesa (PALOP) e aumentou a atração e competitividade internacional da cultura chinesa; e 3) explorar como a China pode formular melhor a sua estratégia de Diplomacia Cultural, de acordo com as exigências da era moderna. O estudo combina os métodos de revisão de literatura, estudo de caso e pesquisa de questionário para explorar os tópicos de diferentes perspetivas com o objetivo de fortalecer a natureza científica dos resultados de investigação. Além da introdução e da conclusão, a tese está dividida em cinco capítulos. O Capítulo 1 discute a conotação e o valor de Diplomacia Cultural (DC). O Capítulo 2 expõe o desenvolvimento e a inovação da Diplomacia Cultural da China (DCC). O Capítulo 3 resume sistematicamente a interação cultural da China no seu processo diplomático com os Países de Língua Oficial Portuguesa (PALOP). O Capítulo 4 discorre sobre o papel do IC em termos do seu modo de operar e dos seus meios diplomáticos. O Capítulo 5 constitui o núcleo da tese e envolve a análise empírica dos dados do estudo de caso e do questionário. Tem como objetivo investigar as funções, a imagem pública, a influência e os meios práticos dos IC no processo de Diplomacia Cultural (DC). As principais descobertas indicam que os IC nos PALOP alcançaram o feedback social ideal e desempenham um papel positivo na formação da imagem da China. No entanto, de acordo com os diferentes continentes onde os IC estão situados, os resultados da pesquisa apresentam caraterísticas distintas que estão intimamente relacionadas com as diferentes políticas externas da China para a América Latina, a Europa e a África e são determinadas pelas experiências históricas e pelas condições nacionais dos vários países. A futura tarefa da Diplomacia Cultural da China (DCC) será a de esclarecer as raízes institucionais da China e os genes culturais por trás do seu desenvolvimento, usando intercâmbios culturais e a cultura fluida da China para transmitir uma mensagem de busca de paz, de desenvolvimento e de cooperação por parte da China.Programa Doutoral em Políticas Pública

    The development of liquid crystal lasers for application in fluorescence microscopy

    Get PDF
    Lasers can be found in many areas of optical medical imaging and their properties have enabled the rapid advancement of many imaging techniques and modalities. Their narrow linewidth, relative brightness and coherence are advantageous in obtaining high quality images of biological samples. This is particularly beneficial in fluorescence microscopy. However, commercial imaging systems depend on the combination of multiple independent laser sources or use tuneable sources, both of which are expensive and have large footprints. This thesis demonstrates the use of liquid crystal (LC) laser technology, a compact and portable alternative, as an exciting candidate to provide a tailorable light source for fluorescence microscopy. Firstly, to improve the laser performance parameters such that high power and high specification lasers could be realised; device fabrication improvements were presented. Studies exploring the effect of alignment layer rubbing depth and the device cell gap spacing on laser performance were conducted. The results were the first of their kind and produced advances in fabrication that were critical to repeatedly realising stable, single-mode LC laser outputs with sufficient power to conduct microscopy. These investigations also aided with the realisation of laser diode pumping of LC lasers. Secondly, the identification of optimum dye concentrations for single and multi-dye systems were used to optimise the LC laser mixtures for optimal performance. These investigations resulted in novel results relating to the gain media in LC laser systems. Collectively, these advancements yielded lasers of extremely low threshold, comparable to the lowest reported thresholds in the literature. A portable LC laser system was integrated into a microscope and used to perform fluorescence microscopy. Successful two-colour imaging and multi-wavelength switching ability of LC lasers were exhibited for the first time. The wavelength selectivity of LC lasers was shown to allow lower incident average powers to be used for comparable image quality. Lastly, wavelength selectivity enabled the LC laser fluorescence microscope to achieve high enough sensitivity to conduct quantitative fluorescence measurements. The development of LC lasers and their suitability to fluorescence microscopy demonstrated in this thesis is hoped to push towards the realisation of commercialisation and application for the technology

    Fuzzy Norm-Explicit Product Quantization for Recommender Systems

    Get PDF
    As the data resources grow, providing recommendations that best meet the demands has become a vital requirement in business and life to overcome the information overload problem. However, building a system suggesting relevant recommendations has always been a point of debate. One of the most cost-efficient techniques in terms of producing relevant recommendations at a low complexity is Product Quantization (PQ). PQ approaches have continued developing in recent years. This system’s crucial challenge is improving product quantization performance in terms of recall measures without compromising its complexity. This makes the algorithm suitable for problems that require a greater number of potentially relevant items without disregarding others, at high-speed and low-cost to keep up with traffic. This is the case of online shops where the recommendations for the purpose are important, although customers can be susceptible to scoping other products. A recent approach has been exploiting the notion of norm sub-vectors encoded in product quantizers. This research proposes a fuzzy approach to perform norm-based product quantization. Type-2 Fuzzy sets (T2FSs) define the codebook allowing sub-vectors (T2FSs) to be associated with more than one element of the codebook, and next, its norm calculus is resolved by means of integration. Our method finesses the recall measure up, making the algorithm suitable for problems that require querying at most possible potential relevant items without disregarding others. The proposed approach is tested with three public recommender benchmark datasets and compared against seven PQ approaches for Maximum Inner-Product Search (MIPS). The proposed method outperforms all PQ approaches such as NEQ, PQ, and RQ up to +6%, +5%, and +8% by achieving a recall of 94%, 69%, 59% in Netflix, Audio, Cifar60k datasets, respectively. More and over, computing time and complexity nearly equals the most computationally efficient existing PQ method in the state-of-the-art

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

    Get PDF
    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Examining interactions among SNPs that can explain the prognostic variability in colorectal cancer

    Get PDF
    Background: Colorectal cancer is a significant medical burden worldwide and in Newfoundland and Labrador. Examining the relationships of SNP interactions with survival outcomes can help identify new prognostic markers for this disease. Objectives: To examine associations between colorectal cancer survival outcomes and interactions of SNPs from MMP family and VEGF interactome genes using data-reduction methods. Methods: Two data-reduction software programs, Cox-MDR and GMDR 0.9, were applied to the data of patients from the Newfoundland Familial Colorectal Cancer Registry. Eight datasets were investigated: one for the MMP gene SNPs (201 SNPs), and seven for the VEGF interaction networks (total 1,517 SNPs). Significance of interaction models was assessed using permutation testing. Associations between significant interaction models and clinical outcomes were confirmed using multivariable regression methods. Results: For the MMP dataset two multi-SNP models and one single-SNP model were identified, while fifteen novel multi-SNP models and thirteen single-SNP models were identified for the VEGF interaction network datasets. All but one of these models were able to distinguish patients based on their outcome risk in multivariable regression models (p-value range: 0.03 – 2.2E-9). Conclusion: This research demonstrated that novel genetic interactions associated with outcome risk in colorectal cancer can be found using data-reduction methods. This proves the utility of these methods in prognostic research
    corecore