3,726 research outputs found

    Undergraduate Catalog of Studies, 2023-2024

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    Trapping, hysteresis and Ostwald ripening in hydrogen storage: a pore-scale imaging study

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    Green hydrogen, produced from surplus electricity during peak production, can be injected into subsurface reservoirs and retrieved during high-demand periods. In this study, X-ray tomography was employed to examine hysteresis resulting from repeated hydrogen injection and withdrawal. An unsteady state experiment was performed to evaluate the distribution of hydrogen and brine after drainage and imbibition cycles: images of the pore-space configuration of fluids were taken immediately once injection had stopped and after waiting for a period of 16 h with no flow. A Bentheimer sandstone sample with a length of 60 mm and diameter of 12.8 mm was used, and hydrogen was injected at ambient temperature and a pore pressure of 1 MPa. The gas flow rate was decreased from 2 ml/min to 0.08 ml/min over three cycles of gas injection followed by water flooding, while the brine injection rate was kept constant. The results showed the presence of capillary pressure hysteresis and hydrogen migration through Ostwald ripening due to the diffusion of gas dissolved in the brine. These phenomena were characterized through analysis of interfacial curvature, area, connectivity and pore occupancy. The hydrogen tended to reside in the larger pore spaces, consistent with water-wet conditions. 16 h after flow had stopped, the hydrogen aggregated into larger ganglia with a single large connected ganglion dominating the volume. Moreover, the Euler characteristic decreased after 16 h, indicating an improvement in connectivity. The work implies that Ostwald ripening – mass transport of dissolved gas – leads to less hysteresis and better connectivity than would be assumed ignoring this effect, as done in assessments of hydrocarbon flow and trapping

    Undergraduate Catalog of Studies, 2023-2024

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

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    Topological data analysis enhanced prediction of hydrogen storage in metal–organic frameworks (MOFs)

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    Metal–organic frameworks (MOFs) have the capacity to serve as gas capturing, sensing, and storing systems. It is usual practice to select the MOF from a vast database with the best adsorption property in order to do an adsorption calculation. The costs of computing thermodynamic values are sometimes a limiting factor in high-throughput computational research, inhibiting the development of MOFs for separations and storage applications. In recent years, machine learning has emerged as a promising substitute for traditional methods like experiments and simulations when trying to foretell material properties. The most difficult part of this process is choosing characteristics that produce interpretable representations of materials that may be used for a variety of prediction tasks. We investigate a feature-based representation of materials using tools from topological data analysis. In order to describe the geometry of MOFs with greater accuracy, we use persistent homology. We show our method by forecasting the hydrogen storage capacity of MOFs during a temperature and pressure swing from 100 bar/77 K to 5 bar/160 K, using the synthetically compiled CoRE MOF-2019 database of 4029 MOFs. Our topological descriptor is used in conjunction with more conventional structural features, and their usefulness to prediction tasks is explored. In addition to demonstrating significant progress over the baseline, our findings draw attention to the fact that topological features capture information that is supplementary to the structural features

    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/

    Indie encounters: exploring indie music socialising in China

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    Indie music, a genre deeply rooted in rock and punk music, is renowned for its independence from major commercial record labels. It has emerged as a choice for music consumers seeking alternatives to mainstream popular music, catering to a niche music preference. The minority nature of indie music not only provides its lovers with a profound space for individual expression and a sense of collective belonging but also introduces other challenges into their social lives. Recently, the field of music sociology has proposed a more diverse perspective to observe and analyse the intricate role of music for individuals and society. In this context, regarding Chinese indie music lovers with niche music preferences, how their indie music practices integrate into their social lives and how they navigate their niche music tastes have become worthwhile topics of exploration. Drawing on interviews with 31 Chinese indie music lovers and extensive online ethnography, this thesis investigates how Chinese indie music lovers comprehend and engage with indie music, and how the power of indie music shapes them and their social behaviours. I employ the theoretical framework of ‘music in action’ (Hennion, 2001; DeNora, 2011, 2016) and symbolic interactionism (Mead, 1934; Goffman, 1959; Blumer, 1969) to examine the dynamic and multifaceted roles of indie music in the social lives of Chinese indie music lovers. I develop a concept of ‘music socialising’ to delve into several key aspects of music lovers’ social practices. I contend that through various forms of musical activities such as music selection, live music attendance, and digital practices, indie music lovers exhibit strategic and reflexive characteristics in their music practices. These practices actively contribute to constructing and maintaining self and identity, negotiating social ties, and forming and mediating collectivity within a broader social landscape. It is through these processes that the music practices of Chinese indie music lovers are endowed with meanings, thereby shaping their social reality. This thesis presents a rich and nuanced picture of the social experiences of Chinese indie music lovers, uncovering the transformative power of their indie music practices. It presents a compelling argument for the significance of music as a social agency, highlighting the complex interactions between music, individuals, and society. By bridging theoretical insights with rich empirical data, this thesis contributes to our understanding of the socio-cultural dimensions of music, offering fresh perspectives on the role of indie music in contemporary Chinese society

    A Near-half-century Simulation of the Solar Corona

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    We present an overview of results from a magnetofrictional model of the entire solar corona over a period of 47 yr. The simulation self-consistently reproduces decades of solar phenomena, varying in duration between rapid eruptions and the long-term solar cycles, from an input of observed active regions emerging at the photosphere. We have developed a geometric approach to use magnetic helicity to identify and localize the frequent eruptions that occur in the simulation. This method allows us to match our results to extreme-ultraviolet observations of transient events. We have analyzed the evolving magnetic topology by computing the squashing factor and segmenting the corona into discrete magnetic domains bounded by the Separatrix-Web. The simulations show a more dynamic structure to the Separatrix-Web than is predicted by potential field models, which may explain solar wind observations

    Single-cell time-series analysis of metabolic rhythms in yeast

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    The yeast metabolic cycle (YMC) is a biological rhythm in budding yeast (Saccharomyces cerevisiae). It entails oscillations in the concentrations and redox states of intracellular metabolites, oscillations in transcript levels, temporal partitioning of biosynthesis, and, in chemostats, oscillations in oxygen consumption. Most studies on the YMC have been based on chemostat experiments, and it is unclear whether YMCs arise from interactions between cells or are generated independently by each cell. This thesis aims at characterising the YMC in single cells and its response to nutrient and genetic perturbations. Specifically, I use microfluidics to trap and separate yeast cells, then record the time-dependent intensity of flavin autofluorescence, which is a component of the YMC. Single-cell microfluidics produces a large amount of time series data. Noisy and short time series produced from biological experiments restrict the computational tools that are useful for analysis. I developed a method to filter time series, a machine learning model to classify whether time series are oscillatory, and an autocorrelation method to examine the periodicity of time series data. My experimental results show that yeast cells show oscillations in the fluorescence of flavins. Specifically, I show that in high glucose conditions, cells generate flavin oscillations asynchronously within a population, and these flavin oscillations couple with the cell division cycle. I show that cells can individually reset the phase of their flavin oscillations in response to abrupt nutrient changes, independently of the cell division cycle. I also show that deletion strains generate flavin oscillations that exhibit different behaviour from dissolved oxygen oscillations from chemostat conditions. Finally, I use flux balance analysis to address whether proteomic constraints in cellular metabolism mean that temporal partitioning of biosynthesis is advantageous for the yeast cell, and whether such partitioning explains the timing of the metabolic cycle. My results show that under proteomic constraints, it is advantageous for the cell to sequentially synthesise biomass components because doing so shortens the timescale of biomass synthesis. However, the degree of advantage of sequential over parallel biosynthesis is lower when both carbon and nitrogen sources are limiting. This thesis thus confirms autonomous generation of flavin oscillations, and suggests a model in which the YMC responds to nutrient conditions and subsequently entrains the cell division cycle. It also emphasises the possibility that subpopulations in the culture explain chemostat-based observations of the YMC. Furthermore, this thesis paves the way for using computational methods to analyse large datasets of oscillatory time series, which is useful for various fields of study beyond the YMC
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