<p> Reduced oxygen tension (i.e. hypoxia) regulates gene expression in various chromaffin cell types that synthesize catecholamines. In this study, the effect of chronic hypoxia on tyrosine hydroxylase (TH) mRNA and protein expression was investigated in the adrenomedullary chromaffin MAH cell line. RT-PCR results indicated that TH mRNA was expressed in MAH cells both during normoxia (20% 0 2) and hypoxia (5% 02). However, TH mRNA expression during chronic hypoxia was significantly higher than that during normoxia, increasing by approximately 2- fold after 16 hour exposure to chronic hypoxia. Western Blot analysis of the regulation of TH gene expression by chronic hypoxia indicated that TH protein initially decreased during 10 hr exposure to hypoxia and this was followed by a rapid increase in expression over the next 10 hr, and then by a slower increase (up to 1.3x initial control) after 72 hr exposure. Therefore, TH mRNA and protein levels were changed in MAH cells by hypoxia in a time-dependent manner. Surprisingly, cobalt treatment of MAH cells, expected to mimic the effects of chronic hypoxia, had little effect on TH gene expression. Interestingly, the decrease in TH expression protein after 10 hr exposure to hypoxia was prevented by nifedipine, an L-type calcium channel blocker. These results suggest that MAH cells represent a useful model system for examining hypoxia-induced gene regulation in an 02-sensitive cell line. Additionally, preliminary studies on HIF-1a expression in MAH cells showed that HIF-la mRNA was expressed and remained stable under both hypoxic and normoxic conditions. </p> / Thesis / Master of Science (MSc)

Immunoassays are widely used for detection of antigens in a wide range of applications including assays in pharmaceutical development. Immunoassays are continuously improved in many aspects including automatization, miniaturization and extending the dynamic range. The need to measure low abundance molecules are challenging and the need to improve the sensitivity is desired. The Gyrolab technology is a miniaturized immunoassay performed in an automated system covering a broad concentration range. In order to  extend the sensitivity, the technology is combined with Binding Oligo Ladder Detection (BOLD) amplification. The technology behind BOLD or Exazym ® utilizes a DNA primer, a polymerase, and a template (RNA) to generate a ladder-like modified DNA strand. Antibodies with affinity for the polymerized DNA:RNA hybrid strand (duplex) conjugated with reporter molecules are introduced to the system, resulting in an increased number of signal-generating molecules associated with each bound analyte molecule. In this thesis, the development of an ultra-sensitive immunoassay is pursued by applying Exazym ® add-on reagents to the Gyrolab platform, comparing performance with the standard Gyrolab sandwich assay and other commercially available high-performing TNF-α assays. The work includes characterization of a wide range of reaction variables involved in the BOLD signal amplification process including hybridization, polymerization, and detection of a synthetic oligonucleotide. The breakthrough involves the introduction of Allophycocyanin (APC) as a fluorescent conjugate, significantly improving sensitivity and signal-to-noise ratios. The BOLD amplified sensitivity for the TNF-α assay approaches levels seen in ultra-sensitive biomarker assays like Erenna ® and Simoa®. Exazym® technology on the Gyrolab platform allows highly sensitive biomarker assays with minimal sample volume and a 1–2-hour run-time. The study marks substantial progress in achieving ultra-sensitive biomarker assays on the Gyrolab platform through BOLD signal amplification. The use of APC-conjugated detection reagents holds promise for future optimization studies.

Yes / In this paper, we present the design of a compact and highly sensitive microwave sensor based on a metamaterial complementary split-ring resonator (CSRR), for liquid characterization at microwave frequencies. The design consists of a two-port microstrip-fed rectangular patch resonating structure printed on a 20 × 28 mm2 Roger RO3035 substrate with a thickness of 0.75 mm, a relative permittivity of 3.5, and a loss tangent of 0.0015. A CSRR is etched on the ground plane for the purpose of sensor miniaturization. The investigated liquid sample is put in a capillary glass tube lying parallel to the surface of the sensor. The parallel placement of the liquid test tube makes the design twice as efficient as a normal one in terms of sensitivity and Q factor. By bending the proposed structure, further enhancements of the sensor design can be obtained. These changes result in a shift in the resonant frequency and Q factor of the sensor. Hence, we could improve the sensitivity 10-fold compared to the flat structure. Subsequently, two configurations of sensors were designed and tested using CST simulation software, validated using HFSS simulation software, and compared to structures available in the literature, obtaining good agreement. A prototype of the flat configuration was fabricated and experimentally tested. Simulation results were found to be in good agreement with the experiments. The proposed devices exhibit the advantage of exploring multiple rapid and easy measurements using different test tubes, making the measurement faster, easier, and more cost-effective; therefore, the proposed high-sensitivity sensors are ideal candidates for various sensing applications. / This work was supported by the Moore4Medical project, funded within ECSEL JU in collaboration with the EU H2020 Framework Programme (H2020/2014–2020) under grant agreement H2020-ECSEL-2019-IA-876190, and the Fundação para a Ciência e Tecnologia (ECSEL/0006/2019). This project received funding in part from the DGRSDT (Direction Générale de la Recherche Scientifique et du Développement Technologique), MESRS (Ministry of Higher Education and Scientific Research), Algeria. This work was also supported by the General Directorate of Scientific Research and Technological Development (DGRSDT)–Ministry of Higher Education and Scientific Research (MESRS), Algeria, and funded by the FCT/MEC through national funds and, when applicable, co-financed by the ERDF, under the PT2020 Partnership Agreement under the UID/EEA/50008/2020 project.

Island biogeography theory predicts that the patterns and distributions of spatially isolated populations are governed by large scale processes. The high elevations forests in the Southern Appalachians represent a series of naturally fragmented islands that harbor many isolated populations of species at the southern limits of their range. Understanding the governing forces of population dynamics in this region will enhance the probability of species persistence in the face of threats such as global warming and human development. We surveyed bird populations across multiple elevations in Virginia and combined this with a multi-scale habitat analysis to determine influences of species presence and species richness. We detected 101 species across the elevation gradient, including 12 species with special conservation status and ten species whose presence increased with increasing elevation. These ten elevation sensitive species responded to habitat variables at both the microhabitat and landscape scale, with species-specific patterns of habitat variable correlation emerging. Habitat type was least effective in predicting species presence for any elevation sensitive species. Species richness declined over the elevation gradient until the highest elevations, where this trend reversed and richness began to increase. This pattern was driven by an increase in short-distance migrants beginning at mid-elevations, which ultimately overpowered a corresponding decrease in long-distance migrants beginning at similar elevations. Habitat analysis linked these patterns to a preference of short-distance migrants for smaller, more isolated non-forested patches, and a historical lack of persistence for long-distance migrants. Conservation and management decisions for the region should focus on a multi-scale approach that preserves all habitat types for continued species presence and high species richness, although the persistence of particular elevation sensitive species is compounded by unique species-habitat relationships and the perception of islands as species-specific. Continued monitoring of these fragmented populations in light of both short- and long-term threats which span multiple scales of influence will maintain high species richness and ensure the persistence of crucial breeding habitat. / Master of Science

Two topics dealing with adhesion are addressed: an investigation of the cling of thin polymeric films and an analysis of the effects of viscoelasticity on adhesive systems involving curvature mismatch. The results of an investigation into the mechanisms of adhesion and debonding energy associated with the cling between polymeric films and various substrates is presented first. The thermodynamic work of adhesion, electrostatic attraction, and substrate roughness apparently play significant roles in the cling of a film to a substrate. Peel tests are conducted and strain energy release rates are determined which show different debonding energies for the various film-substrate systems. In the analysis of adhesive systems involving curvature mismatch, the focus of the work is on modeling the bond behavior using the solution to the beam on a viscoelastic foundation problem. In addition, the behavior of the adhesive is modeled with a recursive technique using a stress distribution obtained from the solution to the beam on an elastic foundation problem. Debond rate tests are described and conducted so that experimental results may be compared with analytical results. For both adhesion topics, the mechanisms and mechanics of adhesion are considered and experimental tests are conducted. / Master of Science

The prevalence of distressing content on social media raises concerns about users' mental well-being, prompting the use of trigger warnings (TW) and content warnings (CW). However, varying practices across platforms indicate a lack of clarity among users regarding these warnings. To gain insight into how users experience and use these warnings, we conducted interviews with 15 regular social media users. Our findings show that users generally have a positive view of warnings, but there are differences in how they understand and use them. Challenges related to using TW/CW on social media emerged, making it a complex decision when dealing with such content. These challenges include determining which topics require warnings, navigating logistical complexities related to usage norms, and considering the impact of warnings on social media engagement. We also found that external factors, such as how the warning and content are presented, and internal factors, such as the viewer's mindset, tolerance, and level of interest, play a significant role in the user's decision-making process when interacting with content that has TW/CW. Participants emphasized the need for better education on warnings and triggers in social media and offered suggestions for improving warning systems. They also recommended post-trigger support measures. The implications and future directions include promoting author accountability, introducing nudges and interventions, and improving post-trigger support to create a more trauma-informed social media environment. / Master of Science / In today's world of social media, you often come across distressing content that can affect your mental well-being. To address this concern, platforms and content authors use something called trigger warnings (TW) and content warnings (CW) to alert users about potentially upsetting content. However, different platforms have different ways of using these warnings, which can be confusing for users. To better understand how people like you experience and use these warnings, we conducted interviews with 15 regular social media users. What we found is that, in general, users have a positive view of these warnings, but there are variations in how they understand and use them. Using TW/CW on social media can be challenging because it involves deciding which topics should have warnings, dealing with the different rules on each platform, and thinking about how warnings affect people's engagement with content. We also discovered that various factors influence how people decide whether to engage with warned content. These factors include how the warning and content are presented and the person's own mindset, tolerance for certain topics, and level of interest. Our study participants highlighted the need for better education about warnings and triggers on social media. They also had suggestions for improving how these warnings are used and recommended providing support to users after they encounter distressing content. Looking ahead, our findings suggest the importance of holding content creators accountable, introducing helpful tools and strategies, and providing better support to make social media a more empathetic and supportive place for all users.

The performance of connections and full-scale shear walls constructed with acrylic foam pressure sensitive adhesive (PSA) tape is the focus of this thesis. The objectives of this study were first to investigate the bonding characteristics of adhesive tape to wood substrates and then to expand this investigation to cover adhesive-based shear walls subjected to high wind and seismic loadings. A total of 287 monotonic connection tests and 23 reversed cyclic wall tests were performed to achieve these objectives. Connection tests were performed in accordance with ASTM D 1761-88 (2000), and walls were tested using the CUREE (Consortium of Universities for Earthquake Engineering) general displacement-based protocol. Variables investigated within the main study were the following: the use of OSB versus plywood sheathing, the effect of priming and surface sanding on adhesion, and the comparison of connections involving mechanical fasteners with those that utilized only adhesive tape or a combination of the two. It was found that an application pressure of 207 kPa (30 psi) or greater was needed to form a sound bond between the acrylic foam adhesive tape and a wood substrate. Properly bonded OSB and plywood connections provided fairly ductile failure modes. Full-scale walls constructed with adhesive tape performed similarly to traditional wall configurations, while walls constructed with a combination of adhesive tape and mechanical fasteners provided significant gains in strength and toughness. The results of this study serve to provide a foundation for expanding the engineering uses of acrylic foam adhesive tape for structural applications. / Master of Science

The focal question to be asked is who are Swedish architects truly building for? If the answer is not an unequivocal ‘everybody’, then the issue at hand makes itself lucid. Historically, our architectural designs have primarily accommodated the able-bodied perspective. Only in the year 2000, with the inception of the national policy ‘’from patient to citizen’’, did regulations begin to address the needs of the physically disadvantaged. However, in this endeavor, a significant portion of our society has been overlooked – those whose neurodiverse conditions impede their participation in spatial environments. Among these, a notable demographic is autistic individuals. Despite being historically marginalized, autism diagnoses have surged by 787% between 1998 and 2018, with approximately 1% of the Swedish population identified as autistic today. This translates to around one hundred thousand citizens whose spatial experiences remain unaccounted for in our architectural considerations. This thesis researches what position autism has in Swedish domestic architecture, and critically looks upon the current laws and regulation surrounding the issue. It analyzes existing case studies to ultimately prove that the very thing these buildings set out to do, they are failing at. In response to these issues, this thesis proposes not only a design framework for architects to adhere to when designing inclusively for autistic people. But also a typological application of said framework as a synthesis project, where the framework is applied to house the existing LSS housing program prevalent in Sweden.

Maude es un lenguaje de programación declarativo basado en la lógica de reescritura que incorpora muchas características que lo hacen muy potente. Sin embargo, a la hora de probar ciertas propiedades computacionales esto conlleva dificultades. La tarea de probar la terminación de sistemas de reesctritura es de hecho bastante dura, pero aplicada a lenguajes de programación reales se concierte en más complicada debido a estas características inherentes. Esto provoca que métodos para probar la terminación de este tipo de programas requieran técnicas específicas y un análisis cuidadoso. Varios trabajos han intentado probar terminación de (un subconjunto de) programas Maude. Sin embargo, todos ellos siguen una aproximación transformacional, donde el programa original es trasformado hasta alcanzar un sistema de reescritura capaz de ser manejado con las técnicas y herramientas de terminación existentes. En la práctica, el hecho de transformar los sistemas originales suele complicar la demostración de la terminación ya que esto introduce nuevos símbolos y reglas en el sistema. En esta tesis, llevamos a cabo el problema de probar terminación de (un subconjunto de) programas Maude mediante métodos directos. Por un lado, nos centramos en la estrategia de Maude. Maude es un lenguaje impaciente donde los argumentos de una función son evaluados siempre antes de la aplicación de la función que los usa. Esta estrategia (conocida como llamada por valor) puede provocar la no terminación si los programas no están escritos cuidadosamente. Por esta razón, Maude (en concreto) incorpora mecanismos para controlar la ejecución de programas como las anotaciones sintácticas que están asociadas a los argumentos de los símbolos. En reescritura, esta estrategia sería conocida como reescritura sensible al contexto innermost (RSCI). Por otro lado, Maude también incorpora la posibilidad de declarar atributos. / Alarcón Jiménez, B. (2011). Towards a Framework for Proving Termination of Maude Programs [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11003

In this dissertation, four distinct but in some ways related topics, mostly related to experimental and theoretical investigations of friction and adhesion of elastomeric materials, are presented. First, an experimental and theoretical study of the interaction between elastic beams and granular media under compressive loading is performed. Buckling loads of beams with different dimensions and boundary conditions within granular media of different depths and grain sizes are measured, and theoretically approximated using the Ritz energy approach, based on the concept of beam on an elastic foundation. Several nondimensional parameters and a scaling law are derived to characterize different interaction regimes between the beams and granular support. The findings from this work is believed to be helpful for improved understanding of interactions between elastic beams and surrounding elastic foundation with applications to piles, oil pipelines, and robotic needle insertion into soft tissues. Second, the role of axial compliance on the friction of extensible strips is investigated. Significant changes were observed in the static and kinetic friction of strips, when the effective axial compliance was changed. The underlying causes of the changes in the frictional response are explained and quantitatively predicted using an extended shear lag model. We believe that this study provides insights into the effect of axial compliance on the frictional response of materials, paving the way for design and optimization of systems where the static and kinetic friction forces play an important role. Third, the effect of normal force and rate on the kinetic friction of two different elastomers, namely acrylic and silicone-based elastomers is evaluated. A custom-built pendulum test setup was used to perform the friction test in dynamic conditions. Two substantially different responses with respect to the change in normal force were observed and the role of different contributions to the frictional response of viscoelastic materials, i.e. bulk hysteresis friction, adhesion friction, and cohesion friction, are discussed. Different scenarios such as modifying the surface by using graphite powder, reducing test velocity, and also performing drop tests to characterize the surface hysteresis of the elastomers, were considered to further explore the origin of frictional responses of the elastomers. This study could improve insights gained from Dynamic Mechanical Analysis (DMA) data when obtaining and interpreting the effect of normal force on kinetic COF of elastomers with potential applications to tires, shoes, etc. where friction plays an important role. Last, a generalized scaling law, based on the classical fracture mechanics approach, is developed to predict the bond strength of adhesive systems. The proposed scaling law, which depends on the rate of change of bond area with compliance, is in apparent discrepancy with the previously reported scaling relationship that depends on the ratio of area to compliance. This distinction can have a profound impact on the expected bond strength of systems, particularly when failure mechanism changes or the compliance of the load train is increased. Furthermore, the shear lag model is implemented to derive a closed-form relation for the system compliance and the conditions where the two models deviate from each other are discussed and demonstrated. The results obtained from this approach could lead to a better understanding of the relationship between the bond strength and the geometry and mechanical properties of adhesive systems, with applications to different types of adhesive joints such as bio-inspired adhesive, biomedical adhesive tapes, and structural adhesive joints. / Ph. D. / In this dissertation, four distinct but in some ways related topics, mostly related to experimental and theoretical investigations of friction and adhesion of elastomeric materials, are presented. The theoretical models are based on classic solutions for load transfer between two members through shearing an adhesive layer or frictional interface on extensible support layers. First, an experimental and theoretical study of buckling of elastic columns embedded in granular media is performed. In many engineering applications, it is desirable to insert and manipulate an elastic column like needle or drill rod within complex media, such as soft tissues or granular beds like sand and gravel. In these procedures the column is subjected to axial loading and it tends to buckle and lose stability due to a high length to thickness ratio. Burrowing a flexible structure through fragile media requires understanding the coupled interactions between a geometrically non-linear structure and its reconfigurable surroundings. Several nondimensional parameters and a scaling law are derived to characterize different interaction regimes between the columns and granular support in order to better understand the stability of elastic structures confined in a granular bed. Second, a comprehensive study that combines theory and experiments to investigate frictional responses of a system, i.e. static and kinetic friction, with change in system stiffness is presented. Friction plays an important role in many technologies such as tires, brakes, rubber seals, conveyer belts, and footwear. Understanding the role of system stiffness on the frictional properties of materials, from both experimental and theoretical points of view, has important implications for such technologies. Significant changes were observed in the static and kinetic friction of strips when the effective axial stiffness was changed. The underlying causes of the changes in the frictional response are explained and quantitatively predicted by a theoretical model. Furthermore, a permanent increase in kinetic friction of sufficiently soft extensible strip was found, with potential application to improved friction performance of materials where the kinetic friction plays a major role. Third, the effect of normal force and rate on the kinetic friction of two different elastomers, namely acrylic and silicone-based elastomers, is evaluated. A custom-built pendulum test setup was used to perform the friction test in dynamic conditions. Two substantially different responses with respect to the change in normal force were observed and the role of different frictional mechanisms is discussed. This study could improve insights gained from mechanical testing data at different temperatures and speed when obtaining and interpreting the effect of normal force on kinetic COF of elastomers, with potential applications to tires, shoes, etc., where friction plays an important role. Last, a theoretical model, to predict the bond strength of adhesive systems, is developed. The proposed model, which depends on the rate of change of bond area with compliance, is in apparent discrepancy with the previously reported scaling relationship thatdepends on the ratio of area to compliance. This distinction can have a profound impact on the expected bond strength of systems, particularly when failure mechanism changes or the compliance of the load train is increased. The conditions where the two models deviate from each other are discussed and demonstrated. The developed model could help to better understand the role of system compliance on the bond strength of adhesive systems such as bio-inspired adhesive, biomedical adhesive, and structural adhesive, where the system stiffness changes significantly depending on the applications.