7,858 research outputs found

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

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    Genomic Tools in Biological Invasions: Current State and Future Frontiers

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    Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community

    Information actors beyond modernity and coloniality in times of climate change:A comparative design ethnography on the making of monitors for sustainable futures in Curaçao and Amsterdam, between 2019-2022

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    In his dissertation, Mr. Goilo developed a cutting-edge theoretical framework for an Anthropology of Information. This study compares information in the context of modernity in Amsterdam and coloniality in Curaçao through the making process of monitors and develops five ways to understand how information can act towards sustainable futures. The research also discusses how the two contexts, that is modernity and coloniality, have been in informational symbiosis for centuries which is producing negative informational side effects within the age of the Anthropocene. By exploring the modernity-coloniality symbiosis of information, the author explains how scholars, policymakers, and data-analysts can act through historical and structural roots of contemporary global inequities related to the production and distribution of information. Ultimately, the five theses propose conditions towards the collective production of knowledge towards a more sustainable planet

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

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    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/

    Location Reference Recognition from Texts: A Survey and Comparison

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    A vast amount of location information exists in unstructured texts, such as social media posts, news stories, scientific articles, web pages, travel blogs, and historical archives. Geoparsing refers to recognizing location references from texts and identifying their geospatial representations. While geoparsing can benefit many domains, a summary of its specific applications is still missing. Further, there is a lack of a comprehensive review and comparison of existing approaches for location reference recognition, which is the first and core step of geoparsing. To fill these research gaps, this review first summarizes seven typical application domains of geoparsing: geographic information retrieval, disaster management, disease surveillance, traffic management, spatial humanities, tourism management, and crime management. We then review existing approaches for location reference recognition by categorizing these approaches into four groups based on their underlying functional principle: rule-based, gazetteer matching–based, statistical learning-–based, and hybrid approaches. Next, we thoroughly evaluate the correctness and computational efficiency of the 27 most widely used approaches for location reference recognition based on 26 public datasets with different types of texts (e.g., social media posts and news stories) containing 39,736 location references worldwide. Results from this thorough evaluation can help inform future methodological developments and can help guide the selection of proper approaches based on application needs

    Hybrid energy system integration and management for solar energy: a review

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    The conventional grid is increasingly integrating renewable energy sources like solar energy to lower carbon emissions and other greenhouse gases. While energy management systems support grid integration by balancing power supply with demand, they are usually either predictive or real-time and therefore unable to utilise the full array of supply and demand responses, limiting grid integration of renewable energy sources. This limitation is overcome by an integrated energy management system. This review examines various concepts related to the integrated energy management system such as the power system configurations it operates in, and the types of supply and demand side responses. These concepts and approaches are particularly relevant for power systems that rely heavily on solar energy and have constraints on energy supply and costs. Building on from there, a comprehensive overview of current research and progress regarding the development of integrated energy management system frameworks, that have both predictive and real-time energy management capabilities, is provided. The potential benefits of an energy management system that integrates solar power forecasting, demand-side management, and supply-side management are explored. Furthermore, design considerations are proposed for creating solar energy forecasting models. The findings from this review have the potential to inform ongoing studies on the design and implementation of integrated energy management system, and their effect on power systems

    iBUST: An intelligent behavioural trust model for securing industrial cyber-physical systems

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    To meet the demand of the world's largest population, smart manufacturing has accelerated the adoption of smart factories—where autonomous and cooperative instruments across all levels of production and logistics networks are integrated through a Cyber-Physical Production System (CPPS). However, these networks are comprised of various heterogeneous devices with varying computational power and memory capabilities. As a result, many secure communication protocols – that demand considerably high computational power and memory – can not be verbatim employed on these networks, and thereby, leaving them more vulnerable to security threats and attacks over conventional networks. These threats can largely be tackled by employing a Trust Management Model (TMM) by exploiting the behavioural patterns of nodes to identify their trust class. In this context, ML-based models are best suited due to their ability to capture hidden patterns in data, learning and improving the pattern detection accuracy over time to counteract and tackle threats of a dynamic nature, which is absent in most of the conventional models. However, among the existing ML-based solutions in detecting attack patterns, many of them are computationally expensive, require a long training time, and a considerably large amount of training data—which are seldom available. An aid to this is the association rule learning (ARL) paradigm, whose models are computationally inexpensive and do not require a long training time. Therefore, this paper proposes an ARL-based intelligent Behavioural Trust Model (iBUST) for securing the CPPS. For this intelligent TMM, a variant of Frequency Pattern Growth (FP-Growth), called enhanced FP-Growth (EFP-Growth) algorithm is developed by altering the internal data structures for faster execution and by developing a modified exponential decay function (MEDF) to automatically calculate minimum supports for adapting trust evolution characteristics. In addition, a new optimisation model for finding optimum parameter values in the MEDF and an algorithm for transmuting a 1D quantitative feature into a respective categorical feature are developed to facilitate the model. Afterwards, the trust class of an object is identified employing the Naïve Bayes classifier. This proposed model is evaluated on a trust evolution-supported experimental environment along with other compared models taking a benchmark dataset into consideration, where it outperforms its counterparts

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    ABC: Adaptive, Biomimetic, Configurable Robots for Smart Farms - From Cereal Phenotyping to Soft Fruit Harvesting

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    Currently, numerous factors, such as demographics, migration patterns, and economics, are leading to the critical labour shortage in low-skilled and physically demanding parts of agriculture. Thus, robotics can be developed for the agricultural sector to address these shortages. This study aims to develop an adaptive, biomimetic, and configurable modular robotics architecture that can be applied to multiple tasks (e.g., phenotyping, cutting, and picking), various crop varieties (e.g., wheat, strawberry, and tomato) and growing conditions. These robotic solutions cover the entire perception–action–decision-making loop targeting the phenotyping of cereals and harvesting fruits in a natural environment. The primary contributions of this thesis are as follows. a) A high-throughput method for imaging field-grown wheat in three dimensions, along with an accompanying unsupervised measuring method for obtaining individual wheat spike data are presented. The unsupervised method analyses the 3D point cloud of each trial plot, containing hundreds of wheat spikes, and calculates the average size of the wheat spike and total spike volume per plot. Experimental results reveal that the proposed algorithm can effectively identify spikes from wheat crops and individual spikes. b) Unlike cereal, soft fruit is typically harvested by manual selection and picking. To enable robotic harvesting, the initial perception system uses conditional generative adversarial networks to identify ripe fruits using synthetic data. To determine whether the strawberry is surrounded by obstacles, a cluster complexity-based perception system is further developed to classify the harvesting complexity of ripe strawberries. c) Once the harvest-ready fruit is localised using point cloud data generated by a stereo camera, the platform’s action system can coordinate the arm to reach/cut the stem using the passive motion paradigm framework, as inspired by studies on neural control of movement in the brain. Results from field trials for strawberry detection, reaching/cutting the stem of the fruit with a mean error of less than 3 mm, and extension to analysing complex canopy structures/bimanual coordination (searching/picking) are presented. Although this thesis focuses on strawberry harvesting, ongoing research is heading toward adapting the architecture to other crops. The agricultural food industry remains a labour-intensive sector with a low margin, and cost- and time-efficiency business model. The concepts presented herein can serve as a reference for future agricultural robots that are adaptive, biomimetic, and configurable

    Runway Safety Improvements Through a Data Driven Approach for Risk Flight Prediction and Simulation

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    Runway overrun is one of the most frequently occurring flight accident types threatening the safety of aviation. Sensors have been improved with recent technological advancements and allow data collection during flights. The recorded data helps to better identify the characteristics of runway overruns. The improved technological capabilities and the growing air traffic led to increased momentum for reducing flight risk using artificial intelligence. Discussions on incorporating artificial intelligence to enhance flight safety are timely and critical. Using artificial intelligence, we may be able to develop the tools we need to better identify runway overrun risk and increase awareness of runway overruns. This work seeks to increase attitude, skill, and knowledge (ASK) of runway overrun risks by predicting the flight states near touchdown and simulating the flight exposed to runway overrun precursors. To achieve this, the methodology develops a prediction model and a simulation model. During the flight training process, the prediction model is used in flight to identify potential risks and the simulation model is used post-flight to review the flight behavior. The prediction model identifies potential risks by predicting flight parameters that best characterize the landing performance during the final approach phase. The predicted flight parameters are used to alert the pilots for any runway overrun precursors that may pose a threat. The predictions and alerts are made when thresholds of various flight parameters are exceeded. The flight simulation model simulates the final approach trajectory with an emphasis on capturing the effect wind has on the aircraft. The focus is on the wind since the wind is a relatively significant factor during the final approach; typically, the aircraft is stabilized during the final approach. The flight simulation is used to quickly assess the differences between fight patterns that have triggered overrun precursors and normal flights with no abnormalities. The differences are crucial in learning how to mitigate adverse flight conditions. Both of the models are created with neural network models. The main challenges of developing a neural network model are the unique assignment of each model design space and the size of a model design space. A model design space is unique to each problem and cannot accommodate multiple problems. A model design space can also be significantly large depending on the depth of the model. Therefore, a hyperparameter optimization algorithm is investigated and used to design the data and model structures to best characterize the aircraft behavior during the final approach. A series of experiments are performed to observe how the model accuracy change with different data pre-processing methods for the prediction model and different neural network models for the simulation model. The data pre-processing methods include indexing the data by different frequencies, by different window sizes, and data clustering. The neural network models include simple Recurrent Neural Networks, Gated Recurrent Units, Long Short Term Memory, and Neural Network Autoregressive with Exogenous Input. Another series of experiments are performed to evaluate the robustness of these models to adverse wind and flare. This is because different wind conditions and flares represent controls that the models need to map to the predicted flight states. The most robust models are then used to identify significant features for the prediction model and the feasible control space for the simulation model. The outcomes of the most robust models are also mapped to the required landing distance metric so that the results of the prediction and simulation are easily read. Then, the methodology is demonstrated with a sample flight exposed to an overrun precursor, and high approach speed, to show how the models can potentially increase attitude, skill, and knowledge of runway overrun risk. The main contribution of this work is on evaluating the accuracy and robustness of prediction and simulation models trained using Flight Operational Quality Assurance (FOQA) data. Unlike many studies that focused on optimizing the model structures to create the two models, this work optimized both data and model structures to ensure that the data well capture the dynamics of the aircraft it represents. To achieve this, this work introduced a hybrid genetic algorithm that combines the benefits of conventional and quantum-inspired genetic algorithms to quickly converge to an optimal configuration while exploring the design space. With the optimized model, this work identified the data features, from the final approach, with a higher contribution to predicting airspeed, vertical speed, and pitch angle near touchdown. The top contributing features are altitude, angle of attack, core rpm, and air speeds. For both the prediction and the simulation models, this study goes through the impact of various data preprocessing methods on the accuracy of the two models. The results may help future studies identify the right data preprocessing methods for their work. Another contribution from this work is on evaluating how flight control and wind affect both the prediction and the simulation models. This is achieved by mapping the model accuracy at various levels of control surface deflection, wind speeds, and wind direction change. The results saw fairly consistent prediction and simulation accuracy at different levels of control surface deflection and wind conditions. This showed that the neural network-based models are effective in creating robust prediction and simulation models of aircraft during the final approach. The results also showed that data frequency has a significant impact on the prediction and simulation accuracy so it is important to have sufficient data to train the models in the condition that the models will be used. The final contribution of this work is on demonstrating how the prediction and the simulation models can be used to increase awareness of runway overrun.Ph.D
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