A G-quadruplex (GQ) is a type of noncanonical nucleic acid structure that can form in regions of nucleic acids rich in guanine nucleotides. The guanine bases form a square planar conformation via Hoogsteen hydrogen bonding. These stacked tetrads have inward-facing carbonyl oxygens, facilitating the coordination of ions. Improper GQ conformations can lead to improper regulation of gene expression, potentially resulting in genetic diseases or cancer. Here, we performed molecular dynamics simulations using the Drude polarizable force field (FF) to gain insight into factors contributing to the stability of two GQs. One is the bcl-2 promoter region GQ, which is implicated in several types of cancer including B-cell lymphoma, and the second is the sc1 RNA GQ, which binds to the Fragile-X Mental Retardation Protein (FMRP) and is implicated in the development of Fragile X Syndrome (FXS). Aberrant bcl-2 GQ conformations result in increased production of the BCL2 protein, which is an apoptosis inhibitor. As such, we aim to characterize the factors stabilizing the GQ for future small-molecule development to prevent apoptosis inhibition and therefore cancer. The FMRP protein functions as a regulator of sc1 conformation to control the translation of proteins required for frontal lobe development. FXS arises from a nonsense mutation that causes the deletion of the C-terminal region of FMRP, rendering it non-function. Therefore, we aim to simulate sc1 when FMRP is bound as well as unbound to provide insight into the types of interactions that must be maintained and therefore mimicked by a small molecule drug. / Master of Science in Life Sciences / DNA is commonly represented as a double helix and RNA is thought of as a simple single stranded, disordered molecule, but DNA and RNA can both adopt more complicated structures. An example of this is the G-quadruplex (GQ), a structure that can form in regions of DNA and RNA that are rich in guanine. These guanine bases form a stable core structure that can act as an "on-off" switch for different processes in the cell. Alterations to GQ structure can lead to dysfunction and different types of disease. Here, we perform atomistic computer simulations to further understand factors that contribute to GQ stability, focusing on two different GQs, one of plays a role in several types of cancer, and the other whose regulation is in Fragile X Syndrome (FXS). Furthermore, we study the Fragile X Mental Retardation Protein, which is what brain cells normally use to regulate expression of proteins needed for frontal lobe development by modulating specific GQ structure. The information from these simulations can be used to potentially develop drugs for these conditions.

Osteoarthritis (OA) is the leading cause of musculoskeletal disability in people and horses, and is characterized by progressive joint degeneration. There is a critical need for a better understanding of disease processes leading to OA in order to develop more efficient therapies. A shared feature among different arthritic conditions is chronic synovitis. Macrophages are the main drivers of synovitis and can display pro-inflammatory (M1) or pro-resolving responses (M2). Macrophages promote joint health through phagocytic and secretory activities; however, when these functions are overwhelmed, macrophages upregulate inflammation, recruiting more cells to counteract damage. Once cell recruitment is efficiently accomplished, macrophages coordinate tissue repair and further resolution of inflammation. Bone marrow mononuclear cells (BMNC) are a source of macrophages used to treat inflammation and produce essential molecules for cartilage metabolism; however, little information exists regarding their use in joints. The studies presented in this dissertation focus on understanding the dual role of macrophages in driving and resolving synovitis and how to harness their therapeutic potential. In the first study, patterns of macrophage phenotypes (M1:M2) in healthy and osteoarthritic equine synovium were compared and correlated with gross pathology, histology, and synovial fluid cytokines. M1 and M2 markers were co-expressed in normal and osteoarthritic joints, varying in intensity of expression according to degree of inflammation. Concentrations of synovial fluid IL-10, a macrophage-produced cytokine that is vital for chondrocyte recovery from injury, was lower in OA joints. The combined findings of this study suggest homeostatic mechanisms from synovial macrophages in OA may be overwhelmed, preventing inflammation resolution. In the second study we investigated the response of BMNC to normal (SF) and inflamed synovial fluid (ISF). BMNC cultured in autologous SF or ISF developed into macrophage cultures that were more confluent in ISF (~100%) than SF (~25%), and exhibited phenotypes that were ultimately similar to cells native to normal joints. BMNC cultured in SF or ISF were neither M1 nor M2, but exhibited aspects of both phenotypes and a regulatory response, characterized by increasing counts of IL-10+ macrophages, decreasing concentrations of IL-1β, and progressively increasing concentrations of IL-10 and IGF-1, all more marked in ISF. These findings suggest that homeostatic mechanisms were preserved over time, and potentially favored by macrophage proliferation. Our data suggest that BMNC therapy could potentiate the macrophage- and IL-10-associated mechanisms of joint homeostasis lost in OA. Finally, using an equine model of synovitis, the last study investigated the response of normal and inflamed joints to autologous BMNC injection. Inflamed joints treated with BMNC showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing numbers of regulatory macrophages and synovial fluid concentrations of IL-10, not observed in saline-treated controls. Autologous BMNC are readily available, downregulate synovitis through macrophage-associated effects, and can benefit thousands of patients with OA. Combined, the results of these studies support the role of macrophage-driven synovial homeostasis and identified a therapeutic way to recover homeostatic mechanisms of synovial macrophages lost during chronic inflammation. Our findings also uncover new research directions and methods for future studies targeting modulation of joint inflammation. / Doctor of Philosophy / Osteoarthritis (OA) is a common cause of joint deterioration in people and horses. Current treatments provide limited recovery of joint function, creating an urgent need for more efficient therapies; however, development of new treatments requires better understanding of the mechanism causing OA. A shared characteristic among many arthritic conditions is long-standing inflammation. Cells called macrophages are the main drivers of joint inflammation and can exert pro- and anti-inflammatory effects. Macrophages promote joint health by clearing aggressor agents and secreting molecules required for optimal joint function. However, when these housekeeping functions are overwhelmed by damage, macrophages drive inflammation recruiting more cells to cope with increased demands for repair. If this process is efficiently accomplished, macrophages then resolve inflammation, recovering joint health. Macrophages in the bone marrow (BMNC - bone marrow mononuclear cells) are used to treat inflammation in several tissues and are known to produce molecules essential for joint health. Although little information exists regarding their use in joints, studies treating different organs suggest it can provide high rewards. The studies presented in this dissertation focused on understanding the dual function of macrophages in driving and controlling joint inflammation, and harnessed their therapeutic potential. In the first study, macrophages were investigated in normal and OA-affected joints, and curiously exhibited a hybrid pro- and anti-inflammatory identity in both groups. The indicators of this mixed identity were more markedly expressed in arthritic joints showing gross inflammation. Low levels of a macrophage-derived anti-inflammatory protein called IL-10 were detected in OA joints. The results of this study suggest that anti-inflammatory mechanisms from macrophages may be overwhelmed in OA-affected joints, preventing inflammation to be resolved, and that recovering this anti-inflammatory function may aid in the treatment of OA. In the second study we investigated how the incubation of BMNC in fluid from normal and inflamed joints affects the response of macrophages. Similar to what we observed in the first study, BMNC incubated in both normal and inflamed joint fluid induced macrophages to develop a hybrid identity that was ultimately similar to native cells from normal joints. Macrophages proliferated more when incubated in fluid from inflamed joints. Macrophages in both groups produced anti-inflammatory effects with high levels of IL-10 that were highest in ISF cultures. These observations suggest that higher proliferation of macrophages in inflamed joint fluid helped preserve anti-inflammatory mechanisms. Therefore, our study suggests that joint injection with BMNC could maximize macrophage- and IL-10-associated mechanisms required to resolve joint inflammation. The third and final study investigated the response of normal and inflamed joints to BMNC injection using a model of joint inflammation in horses. Inflamed joints treated with BMNC showed visual and laboratorial markers of improvement, with increasing numbers of macrophages and concentrations of IL-10 in the joint fluid, which remained lower in joints treated with placebo. BMNC provide means to recover macrophage-associated effects required to control joint inflammation and can benefit thousands of patients with OA. Together, the results of these studies show that macrophages are biased promoters of joint health, leading to inflammation when their anti-inflammatory mechanisms are overwhelmed. Replenishing inflamed joints with healthy macrophages maximizes their anti-inflammatory effects, favoring the recovery of a healthy articular environment.

Investigations of polarization switching over broad time and electric field domains, in various modified Pb-based perovskite ferroelectrics, were systematically performed by ferroelectric switching current transient and bipolar drive P-E responses. Studies were performed from E«Ec to E»Ec, where Ec is the coercive field These investigations have shown the presence of broad relaxation time distributions for the switching process, which can extend over several decades in order of magnitude in time, and where the distribution is strongly dependent on the applied electric field. By performing the study of domain dynamics and polarization switching over extremely broad time domains (10⁻⁸ t < 10² sec), more complete information has been obtained that allows for development of a better mechanistic understanding. Prior polarization kinetics studies have focused on relatively narrow time ranges, and were fit to the Avarami equation, which contains a single relaxation time. However, our broad band width polarization dynamics and frequency relaxation studies have been fit to multiple stretched exponential functions extending over decades of order of magnitude in the time domain. Stretched exponential functions for domain nuclei formation, and for domain variant growth have been found. For example, [001]c, [110]c, and [111]c oriented PZN-4.5%PT crystals, nucleation was found to be a volume process (n=3) rather than just a domain wall restricted process. Consequently, nucleation is heterogeneous. And, growth of a domain variant with reversed polarization was found to be a boundary process (n=2), involving diffuse or rough domain walls. We have extended these studies to various types of ferroelectrics including hard, soft and relaxor types. / Master of Science

This dissertation examines theological liberalism and theological conservatism among U.S. Protestants through the lens of moral psychology research. I argue that this theological division parallels similar divides in politics and in morality, theology having become increasingly intertwined with both over the last century. I analyze perspectives on theological method, doctrines of God, and atonement theologies within texts selected for representativeness and influence. Chapter 1 reviews literature in two scholarly discussions: the historical thesis of a “Two-Party System” among U.S. Protestants since the early twentieth century and the sociological thesis of “culture wars” emerging in the late twentieth century. I synthesize chastened versions of both theses into an account of a process of theological polarization. Chapter 2 presents two frameworks from moral psychology, Cultural-Developmental Theory and Moral Foundations Theory, and explains how these frameworks are used in the following chapters. Chapter 3 analyzes theological method in the selected texts. I find that theological conservatives prioritize an Ethic of Divinity that includes authority and sanctity in their approaches to theological method, while theological liberals appeal largely to care and fairness-as-equality in the context of an Ethic of Autonomy and an Ethic of Community. Chapter 4 analyzes doctrines of God. I find that theological conservatives balance divine authority and sanctity with divine care within the context of an Ethic of Divinity, while theological liberals mostly emphasize care, fairness-as-equality, and liberty in conceptions of God within Ethics of Autonomy and of Community. Chapter 5 analyzes atonement theologies. I find that theological conservatives typically foreground authority, sanctity, care, and fairness-as-proportionality within Ethic of Divinity perspectives, while theological liberals mainly focus on care and fairness-as-equality within Ethics of Autonomy and of Community. Chapter 6 surfaces the sociopolitical relevance of these findings in several areas: stances toward abuse, authoritarianism, and divine otherness; connections of theological outlooks to forms of life and reproductive patterns; and possibilities for building understanding-based empathy using informed responses to theological polarization among U.S. Protestants. I point toward the potential for future work on the implicit moral psychologies of doctrines, transnational aspects of theological polarization, and ethical formation for democratic participation. / 2026-07-10T00:00:00Z

Yes / In this paper, single-element and MIMO microstrip antenna with two pairs of unequal slits is proposed as a circularly polarized antenna with negligible back radiation for 5G mid-band handsets. The unequal pairs of slits are engraved on the antenna patch to guarantee the presence of the circular polarization (CP). The proximity-coupled feeding technique is used to excite the proposed microstrip antenna in order to provide larger antenna -10 dB bandwidth which approaches 10.8% (3.48-3.87 GHz). A novel analysis technique is proposed in this paper that demonstrates the 3D axial ratio pattern in order to generate CP in the broadside direction without affecting the structure of the ground plane which ensures weak back radiation. The 3 dB axial ratio bandwidth (ARBW) is found to be equal to 4.1% extended along the range (3.58-3.73 GHz). To make the design more compatible with the 5G mid-band handsets, the 2 × 2 MIMO structure of the proposed antenna with reduced mutual coupling (less than -20 dB) is also presented in this work. The simulation and measured results are in good agreement, and both verify the CP characteristics and the weak back radiation of the proposed antenna. / This paper is partially funded by British Council “2019 UK-China-BRI Countries Partnership Initiative Programme” with project titled “Adapting to Industry 4.0 Oriented International Education and Research Collaboration”.

With increasing parts of the society being digital and quantum computers developing which can break current encryption methods, there is a stronger need for new methods of encryption to ensure safe communication. The Vernam cipher, which is based on key distribution, is an encryption method which can withstand quantum computers. However, for the Vernam cipher to work, the key to decode the messages has to be distributed safely between the two people in contact. Quantum key distribution (QKD) is a possible way to distribute this key and therefore to ensure secure communication based on fundamental quantum mechanical principles. This thesis studies the implementation of an optical setup node for an entanglement-based QKD network. The report includes a brief overview of the relevant theory of quantum mechanics and quantum information for understanding the subject of quantum communication. Furthermore, QKD is defined and the two different protocols BB84, which is a prepare-and-measure QKD protocol together with E91, an entanglement based QKD protocol, is described. The node is implemented using polarizers, mirrors, beamsplitters, polarizing beamsplitters, waveplates, single-mode fibers and detectors. The purpose is to take a photon with an arbitrary polarization state and divide it into four different photons, each going into detectors measuring the intensity of H, V, D respectively A polarization. The result shows that the implemented setup has to be modified to be able to be used in a real single-photon QKD network. This mainly depends on large intensity losses in the beamsplitters but also that the fiber coupling needs to be increased. Two examples of how this can be done is realigning the components in the setup or increasing the degrees of freedom for the light entering the single-mode fibers connected to the detectors.

Since Ebbesen's seminal work in 1998 observing extraordinary optical transmission (EOT) through nanohole arrays, much research has focused on the role of surface plasmon polaritons (SPPs) in EOT. While the energy and momentum conditions have become clear, no consensus has been reached on the role of incident light polarization. This study presents a simple model that captures Bloch-SPP excitation, including the role of polarization, in general periodic plasmonic structures. Our model predicts that under certain conditions polarization conversion should occur in EOT light transmitted through the nanohole array. We experimentally measure polarization conversion in EOT and compare the experimentally obtained results to the predictions of our model. Using numerical simulations, we tie the far field experimental results to the near field underlying physics described by our model. In using polarization conversion to provide evidence supporting our model, we also establish a novel approach to achieving polarization conversion based on SPPs instead of hole shape or other techniques in literature, and present reasons why this approach to achieving polarization conversion may be better suited for applications in biomedical sensing and optical elements. / Master of Science / In 1998, Ebbesen et al¹ observed that when light is shown on a metal nanofilm perforated with nanoholes more light appears on the other side of the metal film than was incident on the nanoholes. The unexpectedly high transmission of light through the nanohole array was termed extraordinary optical transmission (EOT), and quickly found applications in diverse fields such as biomedical sensing^13,14, energy harvesting^12,31, and nonlinear optics^12–14,24 . As the importance of EOT in applications became clear, interest developed in understanding the fundamental physics involved. Over the next 20 years, researchers showed that the incident light (made up of electromagnetic fields) excites conduction electrons on the surface of the metal film¹¹ . Specifically, the light and the electrons couple to form quasiparticles known as surface plasmon polaritons (SPP) which propagate along the surfaces of the metal film. The SPPs on the back surface of the metal film then radiate free space transmitted light, which is observed as EOT. However, much of the physics involved how SPPs mediate EOT has remained unclear. The first focus of this work is theoretical, presenting a microscopic model for SPP mediated EOT. In contrast to many groups which aim to characterize SPPs from their far field properties, our model focuses on the near field microscopic physics and presents the far field properties as a consequence of the near field physics. Since the near field cannot be probed iv experimentally, we use numerical simulations to both verify our model’s predictions in the near field and predict the properties that should be measured in the far field. The second focus of this work is more applications driven. We notice that our model predicts that under certain conditions SPPs should cause a phenomenon known as polarization conversion to occur, which is when the polarization of the transmitted light is different from the polarization of the incident light. We experimentally measure the predicted polarization conversion, thereby providing substantial experimental evidence in support of our theoretical model. Our novel approach to achieving polarization conversion based on the behavior of SPPs differs substantially from the approaches in literature (usually based on hole shape²⁴). We present the reasons why our SPP-based approach to achieving polarization conversion is more robust to fabrication imperfections than the conventional approaches, and describe how our approach could affect various applications.

This dissertation argues that it is possible to retrieve Aristotle’s conception of political friendship in a manner that is relevant for contemporary democracies. First, I offer an account of Aristotelian political friendship that can respond to various conceptual worries within both Aristotle scholarship and contemporary political philosophy regarding the coherence of an account of "friendship between strangers," that is, friendship among people who do not know each other personally. The first two chapters closely examine Aristotle's conception of political friendship as depicted in various passages in the Nicomachean Ethics and the Politics and develop a clear and robust account of Aristotelian political friendship. Chapter 1 argues for an interpretation of Aristotelian political friendship in terms of what I call the mutual-care model of friendship, as opposed to what I call the modern-narrow model which takes friendship to be a personal and intimate relation. This interpretation of friendship as a relation of mutual care thus creates the conceptual space to respond to the worries regarding the incoherence of political friendship as a concept. Chapter 2 defends the view that Aristotelian political friendship is a form of utility friendship that requires its participants to jointly commit to collectively advantageous political goals. Second, I apply the account of Aristotelian political friendship that I introduced in the first two chapters to contemporary democracies. To this end, Chapter 3 investigates whether members of contemporary democracies have reasons to participate in a relationship of mutual care with their political fellows. I argue that the primitive value of political membership constitutes a reason for every member of a democratic polity to minimally care for their political fellows qua parts of their political community. Chapter 4 examines the relationship between affective polarization and political friendship. I maintain that affective polarization undermines political friendship by concealing the ground of friendship, i.e., the perception of a joint commitment to shared political goals. I argue that political friendship can be reestablished in affectively polarized societies through systematic efforts to raise political fellows' awareness of shared political goals. / 2026-10-04T00:00:00Z

京都大学 / 新制・課程博士 / 博士(理学) / 甲第25107号 / 理博第5014号 / 新制||理||1715(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 田島 治, 教授 中家 剛, 准教授 榎戸 輝揚 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

No description available.