3,817 research outputs found
Brittle-viscous deformation cycles at the base of the seismogenic zone in the continental crust
The main goal of the study was to determine the dynamical cycle of ductile-brittle deformation and to characterise the fluid pathways at different scales of a brittle-viscous fault zone active at the base of the seismogenic crust. Object of analysis are samples from the sinistral strike-slip fault zone BFZ045 from Olkiluoto (SW Finland), located at the site of a deep geological repository for nuclear waste.
Combined microstructural analysis, electron backscatter diffraction (EBSD), and mineral chemistry were applied to reconstruct the variations in pressure, temperature, fluid pressure, and differential stress that mediated deformation and strain localization along BFZ045 across the BDTZ. Ductile deformation took place at 400-500° C and 3-4 kbar, and recrystallized grain size piezometry for quartz document a progressive increase in differential stress during mylonitization, from ca. 50 MPa to ca. 120 MPa. The increase in differential stress was localised towards the shear zone center, which was eventually overprinted by brittle deformation in a narrowing shear zone. Cataclastic deformation occurred under lower T conditions down to T ℠320° C and was not further overprinted by mylonitic creep. Porosity estimates were obtained through the combination of x-ray micro-computed tomography (”CT), mercury intrusion porosimetry, He pycnometry, and microstructural analysis. Low porosity values (0.8-4.4%) for different rock type, 2-20 ”m pore size, representative of pore connectivity, and microstructural observation suggest a relationship to a dynamical cycle of fracturing and sealing mechanism, mostly controlled by ductile deformation. Similarly, the observation from fracture orientation analysis indicates that the mylonitic precursor of BFZ045 played an important role in the localization of the brittle deformation. This thesis highlights that the ductile-brittle deformation cycle in BFZ045 was controlled by transient oscillations in fluid pressure in a narrowing shear zone deforming at progressively higher differential stress during cooling
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/
The development of liquid crystal lasers for application in fluorescence microscopy
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
Communicating a Pandemic
This edited volume compares experiences of how the Covid-19 pandemic was communicated in the Nordic countries â Denmark, Finland, Iceland, Norway, and Sweden. The Nordic countries are often discussed in terms of similarities concerning an extensive welfare system, economic policies, media systems, and high levels of trust in societal actors. However, in the wake of a global pandemic, the countriesâ coping strategies varied, creating certain question marks on the existence of a âNordic modelâ.
The chapters give a broad overview of crisis communication in the Nordic countries during the first year of the Covid-19 pandemic by combining organisational and societal theoretical perspectives and encompassing crisis response from governments, public health authorities, lobbyists, corporations, news media, and citizens. The results show several similarities, such as political and governmental responses highlighting solidarity and the need for exceptional measures, as expressed in press conferences, social media posts, information campaigns, and speeches. The media coverage relied on experts and was mainly informative, with few critical investigations during the initial phases. Moreover, surveys and interviews show the importance of news media for citizensâ coping strategies, but also that citizens mostly trusted both politicians and health authorities during the crisis.
This book is of interest to all who are looking to understand societal crisis management on a comprehensive level.âŻThe volume contains chapters from leading experts from all the Nordic countries and is edited by a team with complementary expertise on crisis communication, political communication, and journalism, consisting of Bengt Johansson, Ăyvind Ihlen, Jenny Lindholm, and Mark Blach-Ărsten.âŻPublishe
Direct measurement of coating thermal noise in the AEI 10m prototype
A thermal noise interferometer for the characterization of thermal noise in high reflectivity mirrors has been commissioned and first direct measurements of coating thermal noise have been performed. This serves as an important step in the improvement of current and future gravitational wave detectors
UNPUBLISHING THE NEWS: AN ASSESSMENT OF U.S. PUBLIC OPINION, NEWSROOM ACCOUNTABILITY, AND JOURNALISTSâ AUTHORITY AS âTHE FIRST DRAFT OF HISTORYâ
Unpublishing, or the manipulation, deindexing, or removal of published content on a news organizationâs website, is a hotly debated issue in the news industry that disrupts fundamental beliefs about the nature of news and the roles of journalists. This dissertationâs premise is that unpublishing as a phenomenon challenges the authority of journalism as âthe first draft of history,â questions the assumed relevance of traditional norms, and creates an opportunity to reconsider how news organizations demonstrate their accountability to the public. The study identifies public opinions related to unpublishing practices and approval of related journalistic norms through a public opinion survey of 1,350 U.S. adults. In tandem, a qualitative analysis of 62 editorial policies related to unpublishing offers the first inventory and assessment of emerging journalistic practices and the normative values journalists demonstrate through them. These contributions are valuable to both the academy and the news industry, as they identify a path forward for future research and provide desired guidance to U.S. news organizations. Findings suggest that in response to the unpublishing phenomenon, American journalists defend their professionalism primarily through the traditional professional paradigm of accuracy, invoking it to legitimize new guidelines whether those policies permitted or denounced unpublishing as a newsroom practice. Findings also show newsrooms are pledging increased levels of accountability to their communities and society at large, but how they might demonstrate that accountability more tactically was absent from policy discourse. In addition, both American adults and news organizations place a high value on the accuracy of previously published news content, yet the groupsâ temporal conceptions of accuracy must be reconciled. Ultimately, the unpublishing phenomenon presents an opportunity for journalists to redefine their notions of accountability to their communities. Based on these findings, the study concludes with a call for American news organizations to abandon claims as the âfirst draft of historyâ in the digital era and assume the role of information custodians, proactively establishing and managing the lifecycle of content.Doctor of Philosoph
Investigating the learning potential of the Second Quantum Revolution: development of an approach for secondary school students
In recent years we have witnessed important changes: the Second Quantum Revolution is in the spotlight of many countries, and it is creating a new generation of technologies.
To unlock the potential of the Second Quantum Revolution, several countries have launched strategic plans and research programs that finance and set the pace of research and development of these new technologies (like the Quantum Flagship, the National Quantum Initiative Act and so on).
The increasing pace of technological changes is also challenging science education and institutional systems, requiring them to help to prepare new generations of experts.
This work is placed within physics education research and contributes to the challenge by developing an approach and a course about the Second Quantum Revolution. The aims are to promote quantum literacy and, in particular, to value from a cultural and educational perspective the Second Revolution.
The dissertation is articulated in two parts. In the first, we unpack the Second Quantum Revolution from a cultural perspective and shed light on the main revolutionary aspects that are elevated to the rank of principles implemented in the design of a course for secondary school students, prospective and in-service teachers. The design process and the educational reconstruction of the activities are presented as well as the results of a pilot study conducted to investigate the impact of the approach on students' understanding and to gather feedback to refine and improve the instructional materials.
The second part consists of the exploration of the Second Quantum Revolution as a context to introduce some basic concepts of quantum physics. We present the results of an implementation with secondary school students to investigate if and to what extent external representations could play any role to promote studentsâ understanding and acceptance of quantum physics as a personal reliable description of the world
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
Mathematical Problems in Rock Mechanics and Rock Engineering
With increasing requirements for energy, resources and space, rock engineering projects are being constructed more often and are operated in large-scale environments with complex geology. Meanwhile, rock failures and rock instabilities occur more frequently, and severely threaten the safety and stability of rock engineering projects. It is well-recognized that rock has multi-scale structures and involves multi-scale fracture processes. Meanwhile, rocks are commonly subjected simultaneously to complex static stress and strong dynamic disturbance, providing a hotbed for the occurrence of rock failures. In addition, there are many multi-physics coupling processes in a rock mass. It is still difficult to understand these rock mechanics and characterize rock behavior during complex stress conditions, multi-physics processes, and multi-scale changes. Therefore, our understanding of rock mechanics and the prevention and control of failure and instability in rock engineering needs to be furthered. The primary aim of this Special Issue âMathematical Problems in Rock Mechanics and Rock Engineeringâ is to bring together original research discussing innovative efforts regarding in situ observations, laboratory experiments and theoretical, numerical, and big-data-based methods to overcome the mathematical problems related to rock mechanics and rock engineering. It includes 12 manuscripts that illustrate the valuable efforts for addressing mathematical problems in rock mechanics and rock engineering
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