6,593 research outputs found
Numerical Simulations of Cavitating Bubbles in Elastic and Viscoelastic Materials for Biomedical Applications
The interactions of cavitating bubbles with elastic and viscoelastic materials play a central role in many biomedical applications. This thesis makes use of numerical modeling and data-driven approaches to characterize soft biomaterials at high strain rates via observation of bubble dynamics, and to model burst-wave lithotripsy, a focused ultrasound therapy to break kidney stones.
In the first part of the thesis, a data assimilation framework is developed for cavitation rheometry, a technique that uses bubble dynamics to characterize soft, viscoelastic materials at high strain-rates. This framework aims to determine material properties that best fit observed cavitating bubble dynamics. We propose ensemble-based data assimilation methods to solve this inverse problem. This approach is validated with surrogate data generated by adding random noise to simulated bubble radius time histories, and we show that we can confidently and efficiently estimate parameters of interest within 5% given an iterative Kalman smoother approach and an ensemble- based 4D-Var hybrid technique. The developed framework is applied to experimental data in three distinct settings, with varying bubble nucleation methods, cavitation media, and using different material constitutive models. We demonstrate that the mechanical properties of gels used in each experiment can be estimated quickly and accurately despite experimental inconsistencies, model error, and noisy data. The framework is used to further our understanding of the underlying physics and identify limitations of our bubble dynamics model for violent bubble collapse.
In the second part of the thesis, we simulate burst-wave lithotripsy (BWL), a non- invasive treatment for kidney stones that relies on repeated short bursts of focused ultrasound. Numerical approaches to study BWL require simulation of acoustic waves interacting with solid stones as well as bubble clouds which can nucleate ahead of the stone. We implement and validate a hypoelastic material model, which, with the addition of a continuum damage model and calibration of a spherically- focused transducer array, enables us to determine how effective various treatment strategies are with arbitrary stones. We present a preliminary investigation of the bubble dynamics occurring during treatment, and their impact on damage to the stone. Finally, we propose a strategy to reduce shielding by collapsing bubbles ahead of the stone via introduction of a secondary, low-frequency ultrasound pulse during treatment.</p
Converging organoids and extracellular matrix::New insights into liver cancer biology
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/
Southern Adventist University Undergraduate Catalog 2023-2024
Southern Adventist University\u27s undergraduate catalog for the academic year 2023-2024.https://knowledge.e.southern.edu/undergrad_catalog/1123/thumbnail.jp
Beam scanning by liquid-crystal biasing in a modified SIW structure
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
Systemic Circular Economy Solutions for Fiber Reinforced Composites
This open access book provides an overview of the work undertaken within the FiberEUse project, which developed solutions enhancing the profitability of composite recycling and reuse in value-added products, with a cross-sectorial approach. Glass and carbon fiber reinforced polymers, or composites, are increasingly used as structural materials in many manufacturing sectors like transport, constructions and energy due to their better lightweight and corrosion resistance compared to metals. However, composite recycling is still a challenge since no significant added value in the recycling and reprocessing of composites is demonstrated. FiberEUse developed innovative solutions and business models towards sustainable Circular Economy solutions for post-use composite-made products. Three strategies are presented, namely mechanical recycling of short fibers, thermal recycling of long fibers and modular car parts design for sustainable disassembly and remanufacturing. The validation of the FiberEUse approach within eight industrial demonstrators shows the potentials towards new Circular Economy value-chains for composite materials
Organic Bioelectronics Development in Italy: A Review
In recent years, studies concerning Organic Bioelectronics have had a constant growth due to the interest in disciplines such as medicine, biology and food safety in connecting the digital world with the biological one. Specific interests can be found in organic neuromorphic devices and organic transistor sensors, which are rapidly growing due to their low cost, high sensitivity and biocompatibility. This trend is evident in the literature produced in Italy, which is full of breakthrough papers concerning organic transistors-based sensors and organic neuromorphic devices. Therefore, this review focuses on analyzing the Italian production in this field, its trend and possible future evolutions
Exploring communication and collective behaviour between spatially organised inorganic protocell communities
A living system profoundly relies on mass, information and energy interactions through cell-cell and cell-environment networks. As a step towards understanding such interactions, it is beneficial to design and create bottom-up artificial living systems from non-living components, with a specific focus on synergistic interactivity between artificial cells (protocells) and their local environment. Although there are several routes for fabricating protocellular systems, we recognise key challenges associated with a) developing protocellular models with high levels of organisational tunability, b) achieving cell-environment bilateral communication, and c) realising autonomous self-assembly and regulation of protocell systems. The aim of this thesis is thus to review some matrix-based and matrix-free methods of inorganic protocell (colloidosome) 3D-spatial organisation, as judicious system designs capable of cell-cell and cell-environment communication, collective behaviours, and dynamic self-assembly, in close relation with local environments.The first experimental chapter details assembly of colloidosomes within hydrogel or coacervate-based matrices. A droplet microfluidic technique is employed as a novel method for encapsulating segregated colloidosome colonies within alginate hydrogel microspheres. The technique exploits high tunability for customisable size, ratio, microscale geometry, and 3D-patterning parameters. Benefiting from the versatility associated with such matrix-based systems, the second experimental chapter develops 3D-organised colloidosomes for collective signalling and emergent behaviours. Notably, spatially segregated colonies show proximity-mediated chemical communication with increased kinetics compared to analogous homogenous arrangements. This proximity-enhanced colloidosome signalling is exploited, alongside segregated ionic/covalent crosslinking transitions in the environment, to obtain simultaneous structural degradation and resilience of hydrogel hemispheres as a programmable mechanism for protocell ejection. Colloidosomes are also employed as simple signalling hotspots within coacervate-matrix systems. The final experimental chapter aims to re-imagine colloidosome organisation into a matrix-free system, capable of dynamic self-assembly and self-sorting via electrostatically-active membrane appendages. Alginate-coated and chitosan-coated colloidosomes are either co-assembled or self-sorted, in response to varied pH environments. Again, these systems are highly coordinated with their environment and as such, can be spatially pattered according to temporal pH changes through endogenous enzyme catalysis. Furthermore, a spatiotemporal effect on the rate of colloidosome communication in the presence of a hostile guest molecule is demonstrated. <br/
Selected problems of materials science. Vol. 2. Nano-dielectrics metals in electronics. Mеtamaterials. Multiferroics. Nano-magnetics
The textbook examines physical foundations and practical application of current electronics materials. Modern theories are presented, more important experimental data and specifications of basic materials necessary for practical application are given. Contemporary research in the field of microelectronics and nanophysics is taken into account, while special attention is paid to the influence of the internal structure on the physical properties of materials and the prospects for their use. English-language lectures and other classes on the subject of the book are held at Igor Sikorsky Kyiv Polytechnic Institute at the departments of “Applied Physics” and “Microelectronics” on the subject of materials science, which is necessary for students of higher educational institutions when performing scientific works.
For master’s degree applicants in specialty 105 “Applied physics and nanomaterials”.Розглянуто фізичні основи та практичне застосування актуальних матеріалів електроніки. Подано сучасні теорії, наведено найважливіші експериментальні дані та специфікації основних матеріалів, які потрібні для практичного застосування. Враховано сучасні дослідження у галузі мікроелектроніки та нанофізики, при цьому особливу увагу приділено впливу внутрішньої структури на фізичні властивості матеріалів і на перспективи їх використання. Англомовні лекції та інші види занять за тематикою книги проводяться в КПІ ім. Ігоря Сікорського на кафедрах «Прикладна фізика» та «Мікро-електроніка» за напрямом матеріалознавство, що необхідно студентам вищих навчальних закладів при виконанні наукових робіт.
Для здобувачів магістратури за спеціальністю 105 «Прикладна фізика та наноматеріали»
Characterising natural ventilation through open windows in the presence of wind: a theoretical and experimental investigation into the interaction between window geometry and environmental forces, and its application to envelope flow models of natural ventilation
Natural ventilation systems utilise pressure differentials that arise from wind and buoyancy forces to drive air through buildings. Natural ventilation is typically described using envelope flow models. These are used to size window openings at the design stage, and to predict the annual dynamic thermal performance of buildings. However, envelope flow models rely on highly idealised descriptions of flow through ventilation openings, which do not model realistic window geometries encountered in practice, and assume that ambient air is static. When envelope flow models are applied to building design, inadequate accounting for phenomena relating to wind and opening geometry can lead to under-sized ventilation openings and under-performing buildings.
This thesis develops empirical models that characterise the effect of wind and window geometry on ventilation rates through square orifices and square, hinged openings. To ensure that these models can be applied in the design case to an arbitrary building geometry, these models are characterised using conditions local to the opening. Here the effect of wind is accounted for by a simulated cross-flow parallel to the building façade, and dimensional scaling arguments are applied to develop empirical models of wind driven phenomena based on similarity theory. Three experimental conditions are modelled: still-air tests that measure the ventilation capacity of an opening in idealised conditions; local pressure tests that measure the wind-induced static pressure differential over an opening when no flow occurs through that opening; and dynamic flow tests that measure the ventilation capacity of an opening between these limits.
To validate the use of these local-scale models in building design, this work is then extended to predict the ventilation in a simple two-zone building. This requires the measurement of the speed and direction of the cross-flow on the building façades, and to that end a novel probe is developed that enables simultaneous measurements of these parameters. Wind-tunnel experiments are then used to measure the ventilation rate achieved in the model building, and the results are compared against the predictions of the local-scale window-characterisation models developed in this thesis. The results show an improvement over current models, which tend to overestimate ventilation rates.
This thesis shows that free area models, which are widely used to predict the ventilation capacity of windows, tend to systematically overestimate ventilation rate through simple hinged openings in still air. The Empirical Effective Area Model described in this thesis can be used to predict idealised discharge coefficients with a coefficient of determination of 0.98, compared to 0.57-0.74 for free area models.
A wind-driven cross-flow is shown to interact with window geometry to alter the local pressure field over the surface of an opening. This thesis develops experimental techniques to characterise this change in pressure using a local pressure coefficient. This is used to specify a local dimensionless pressure which is shown to describe the transition between inflow and outflow through an opening. Empirical equations are developed that characterise the local pressure coefficient for square hinged windows as a function of flow approach angle and opening angle, with a coefficient of determination of 0.98.
The generation of non-zero local pressure coefficients is shown to result in orifice discharge coefficients that tend to ±∞ as the dimensionless room pressure tends to zero. Dimensional analysis is used to suggest the total dimensionless volume flow rate as an alternative metric to characterise the ventilation capacity of an opening. This is shown to tend to the idealised discharge coefficient in still-air conditions, and to tend to zero as the local dimensionless pressure tends to zero. The total dimensionless volume flow rate is shown to be finite across the whole range of potential local dimensionless pressure values, and holds positive values for outflow and negative values for inflow. Empirical models are developed to predict the total dimensionless volume flow rate through a square orifice and a square, hinged window as a function of local dimensionless pressure, flow approach angle and opening angle. Coefficients of determination are between 0.975 and 0.984 for the hinged window and between 0.993 and 0.995 for the square orifice, depending on the opening direction and the direction of flow through the opening.
The speed and direction of the cross-flow on the façade of a model cube in a simulated atmospheric boundary layer were measured using the novel cross-flow probe developed in this thesis. Here, mean cross-flow speeds measured with the novel probe agree well with hot-wire measurements. The cross-flow measurements reveal a tetra-modal distribution in façade cross-flow direction, which interacts with a uni-modal variation in cross-flow speed to generate bi-modal distributions in the x and y velocity components at all measured wind angles. This data is used to generate profiles of mean cross-flow speed and mean façade cross-flow direction with wind angle, which are used as inputs to the empirical equations developed to describe the total dimensionless volume flow rate through isolated window openings.
The empirical models used to describe the total dimensionless volume flow rate through isolated windows is used to predict measured ventilation rates in a model building with an internal partition, with a coefficient of determination between 0.94 and 0.99, depending on the ventilation configuration. This compares with coefficients of determination between -0.4 and 0.08 found when applying a conventional orifice flow model. Conventional orifice flow models are predicted to provide good estimates of net volume flow rates through buildings with simple orifice-type openings when the internal resistance is lower than that of either of the external openings. As the internal resistance increases, the orifice flow equation is predicted to increasingly overestimate net volume flow rates.
This work contributes to knowledge by: quantifying the systematic errors arising from the use of free area models common to natural ventilation design; developing an empirical model that describes an idealised discharge coefficient of a family of hinged openings as a function of geometric parameters; identifying novel dimensionless parameters that characterise the change in static pressure across an opening that results from the interaction between wind and window geometry; developing experimental techniques that provide a simple and unambiguous measurement of the local pressure coefficient; experimentally and empirically describing the aerodynamic performance of a simple, square, hinged window in wind-driven conditions; developing a cross-flow probe that can measure the instantaneous speed and direction of wind-driven flow over the surface of a building; quantifying the systematic errors associated with the use of a range of calculation methodologies used to estimate the ventilation rate in a simple model building; and providing practical design guidance to minimise the effect of calculation errors that arise from the use of conventional envelope flow models in wind-driven conditions, when adequate data to describe the phenomena is unavailable
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