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Compositae plants of the genus Erigeron have ca. 390 species, widely distributed in in most temperate regions around the world. Erigeron annus (L.) Pers. (fleabane) is one of the most valuable plants in the genus, used in Chinese folk medicine to treat indigestion, malaria, enteritis, hepatitis and hematuria increasingly since the 1970s. However it is not an indigenous species in China and has not been officially recorded in the Chinese Pharmacopeia. Very little research has been published on it biological activity and no activity against MRSA has been reported. In this research, whole plant material was collected in Shanghai, China and its chemical composition, antibacterial activity, DNA gyrase inhibitory activity and mutagenicity assessment were evaluated on isolated compounds and extracts.

A new conjugate gradient method (the LS method) that takes into account the effect of inexact line searches is introduced and its implementations discussed. The connections between existing conjugate gradient methods and the LS method are used to provide a new explanation of the difference in efficiency between conjugate gradient methods.

Exportin-1 (XPO1) is an essential regulator of cellular nuclear export that traffics hundreds of cargo proteins from the nucleus into the cytoplasm. Nearly three decades of research led to a detailed understanding of the mechanisms underlying XPO1-mediated transport, and this knowledge generated many XPO1-targeting small molecule probes that validated the therapeutic potential of drugging nucleocytoplasmic trafficking. More recently, growing evidence has implicated XPO1 in other functions, including in the coordination of mitotic events, regulation of gene transcription, and formation of biomolecular condensates. These functions operate independently of nuclear export and implicate XPO1 as a broad regulator of many cellular functions. In this work, we demonstrate that many structural classes of electrophilic small molecules target XPO1 at cysteine 528 to suppress T cell activation. In contrast to known cytotoxic XPO1 modulators such as Leptomycin B and the FDA-approved Selinexor, we identify a new class of “Selective Inhibitors of Transcriptional Activation” (SITAs) that display potent inhibition of T cell function with minimal impacts on XPO1-mediated nuclear export, mitotic regulation, and cell viability. To assess how SITAs suppress T cell activation despite their muted effects on nuclear export, we provide evidence that XPO1 scaffolds transcription factors of the NF-κB, AP-1, and NFAT families during T cell activation. SITAs selectively disrupt XPO1 occupancy at euchromatic regions to indirectly abrogate the chromatin localization of NFAT, thereby suppressing T cell activation without affecting cell viability. Beyond the transcription factors that are critical for T cell function, we further demonstrate that the p300 histone acetyltransferase shares many chromatin occupancy sites with XPO1. Targeted modulation of XPO1 by SITAs or small molecule degraders indirectly suppresses p300 chromatin binding and activity, providing a potential mechanistic link between XPO1 and global chromatin accessibility. Our work establishes XPO1 as a bona fide chromatin factor that is essential for the localization of many epigenetic regulators. We propose that new classes of small molecule XPO1 probes with divergent cellular activity profiles can unravel the non-canonical functions of XPO1 to expand its rich underlying biology and therapeutic opportunities beyond nuclear export.

With the advances in low-cost reliable electronic devices, autonomous multi-agent systems play an important role in a wide range of applications, such as sensing networks, smart grid, smart transportation, and exploration in hazardous situations. In recent years, factors such as avoiding a single failure point, demand for privacy preservation, and opting for lower computation and communication costs have created the expectation that the autonomous multi-agent systems should be operated in a distributed manner with no central control. In many operations, coordinating tasks among autonomous multi-agent systems involve some forms of distributed leader-following problems. That is, it is expected that a group of networked autonomous agents, normally referred to as followers, should use their local information and local interactions with their neighboring agents to determine their actions so that the entire network achieves a desired system-level behavior that depends on the state(s) of single or multiple leaders. When the dynamics of the leader(s) is unknown, e.g., in target tracking problems, and only a subset of the agents can measure the state(s) of the leader(s) online, the limited information increases the challenge to meet leader-following objectives. The focus of this dissertation is providing practical leader-following solutions that require the least possible assumptions on the dynamics of the leader(s). More specifically, we consider four types of leader-following objectives. The first problem addressed is a single leader-following problem for a group of heterogeneous linear time-invariant followers, where a subset of the followers has access to the state of an unknown leader in only specific sampling times. We propose a distributed control that uses a minimum-energy control framework to enable the followers to arrive at the sampled state of the leader by the time the next sample arrives. The next problem we consider is a containment control problem, a leader-following problem with multiple leaders, where a group of mobile agents aim to stay in the convex hull spanned by a group of moving leaders with unknown dynamics. Our proposed distributed control enables a group of networked unicycle mobile agents to track the convex hull of the leaders. This algorithm requires the agents to only communicate with each other in discrete-time fashion. The innovation in our containment control design is to model the problem in the form of an active average consensus problem, for which we also propose a novel distributed solution both in continuous-time and discrete-time form. Active average consensus by itself constitutes the third leader-following problem that we study, in which a set of networked agents aim to track the average of the dynamic signals measured by the active agents. The fourth leader-following problem we consider in this dissertation is a coverage problem via a set of mobile agents for a group of dense dynamic targets whose distribution in the space is not known a priori. For this problem, we propose a novel distributed coverage control that first uses a distributed estimation process to enable all the agents to obtain an estimate of the targets' distribution when only a subset of agents in the network can observe the targets. Then, we develop a distributed deployment solution that enables the agents to re-position themselves in a way that their collective quality of service (QoS) distribution is in close accordance with the estimated density distribution of the targets. In our setting, the agents are heterogeneous in the sense that their spatial QoS distribution is different. We demonstrate our results for event detection via sensor networks and UAV-aided wireless communication coverage problems.

With smartphones are ubiquitous, mobile augmented reality systems (MARS) open various opportunities for users to experience and interact with virtual information at physical locations. This study aims to understand how users domesticated Pokemon Go, a MARS which could be seen as the first normalizing MARS for the masses, into their everyday life. A triangulation method combined a participant observation in Kaohsiung, Taiwan and a qualitative content analysis from a popular Taiwanese Facebook Group Page to learn patterns and motivations of the MARS experience. Results show that content is crucial to using the MARS. The MARS facilitates users’ socialization and companionship needs as well as adds a “layer of fun” for its users when they navigate places. A “See What I See” MARS is designed based on the primary research findings on users’ companionship needs from their social networks and from their mobile media. It is a user-generated situated documentary MARS for users to use in everyday life. A prototype was built and tested. Results show that users report the MARS is highly easy to use and usefulness. It enhances users’ experiences in a positive way. Users feel positive companionship from their friends and family members when they use the MARS.

The goal of this research is to provide empirical results that can be used to guide decisions regarding treatments/interventions. This work focuses on two different problems of interest in comparative effectiveness research. The first problem is to understand if the proportion of an event changes over time, when the populations are nested within each other. This often happens in the health care system and is illustrated here by a study of hospital readmissions within 48 hours of a first visit to an emergency department (ED). The nested structure of the data must be taken into account at the analysis stage and there are no standard statistical methods for doing this. We propose a likelihood ratio test based on the product of conditional probabilities in the form of generalized mixed model. This test accommodates conditionality, within subject dependence and between hospital cluster effects. Simulations show that it preserves the type-I error level given no difference, and provides estimates that are less biased in the presence of a large cluster effect. This approach can be implemented using SAS PROC NLMIXED making it easy to apply in this setting. The second problem focuses on the identification of subgroups within a clinical trial, with the goal being the identification of subjects who benefit from the treatment of interest. The focus is on the use of interaction trees which are an extension of the classification and regression trees (CART). The use of interaction trees overcomes both the subjectivity and multiple comparisons that plague a conventional subgroup analysis. However, the method is greedy in finding each local node by exhausting every predictor and its available values. We propose a greediness reduction interaction tree (GRIT) algorithm that integrates random forests and the evolutionary algorithm into the interaction trees. Simulations show that this proposed method outperforms the interaction trees without accessing every predictor given the interaction. The strengths of the proposed method are demonstrated through a real data example from the Biological Markers for Recovery of Kidney (BioMaRK) study. Public Health Significance: Two methodologies proposed provide less bias and more accurate information under certain circumstances. One is for medical and public policy decisions based on administrative datasets and the other is for finding subgroups and generating hypotheses for future clinical trials.

This paper proposes a novel distributed authentication system that uses robust alternatives in cryptographic algorithms to grant a third-party access to personal data without compromising a user's credentials. The paper examines briefly the concept of distributed authentication systems, and discusses how elliptic curve cryptography and Lamport's hash chain can operate in a zero-knowledge proof to establish and manage trust. The paper also discusses how this design avoids some of the most common flaws in distributed authentication systems. Finally, based on results from tests conducted with included source codes, the paper argues that increasing number of rounds of zero-knowledge proof yields substantially faster performance than increasing the modulus for elliptic curve calculations while maintaining comparable levels of security.

Cardiolipin is a phospholipid with negatively charged headgroups. This lipid is structurally unique in its quadruple-chained configuration and functionally unique in its nearly exclusive involvement in the cellular energy production processes. Whether the structural uniqueness leads to the functional exceptionality has long been an open question. Like other phospholipids, cardiolipin is a liquid crystal and demonstrates polymorphism when it is purified and mixed with water. Many studies have been dedicated to examining the phase behavior of cardiolipin liquid crystals in an effort to understand the driving forces behind phase transitions and to ultimately decipher the structure-function relation. However, few, if any, studies have thus far systematically investigated cardiolipin phase behavior in broad temperature and concentration ranges. In this thesis, small- and wide-angle X-ray scattering techniques were employed to study the phase behavior of cardiolipin-water mixtures. A phase diagram was mapped in lipid concentrations from 32.9 wt% to 85.4 wt% and temperatures from -20 °C to 60 °C. Two striking features were observed in this cardiolipin phase diagram: the presence of a lamellar-lamellar phase separation region and a phase displaying crystalline-like X-ray scattering patterns. Based on the X-ray scattering data underlying the phase diagram, electron density maps of the cardiolipin liquid crystals were reconstructed with two different methods and their structural parameters were derived, both within and across a phase boundary. A relationship between phase behavior and structure was observed from this structural information and utilized to construct a "structure map". Based on the structure map, an energetics view was provided to explain the observed phase transitions and to explore the nature and origins of the two striking phase behaviors.

This thesis explores the identity formation of 1949 Chinese immigrants to Taiwan and their descendants through the close examination of their personal experience narratives. The current population of Taiwan is the result of two major waves of immigration from the Chinese mainland: the first wave immigrating roughly 300 years ago; the second in 1949 when the Nationalist government fled to Taiwan. These two distinct populations have different cultural traditions, including food, traditional celebrations, speech patterns, and other aspects of culture. Personal experience narratives are rich vehicles for gaining insight into the identity issues highlighted by these differences. The main focus of the study is a series of personal narratives collected from a 1949 Chinese immigrant family that, as a case study, exemplify the process of the formation of generational identity. The results of the investigation suggest that the identity of first generation immigrants as non-Taiwanese is almost non-negotiable in their narratives, expressed in part by their nostalgic feelings for mainland China. This contrasts with the dynamics of fluidity and stability of the identity/identities of the second and third generation Mainlanders, reflecting a lessening of social boundaries and other social shifts in Taiwan.

Clinical wavefront-guided corneal ablation has been now the most technologically advanced method to reduce the dependence of glasses and contact lenses. It has the potential not only to eliminate spherocylindrical errors but also to reduce higher-order aberrations (HOA). Recent statistics show that more than 96% of the patients who received laser in situ keratomileusis (LASIK) treatment reported their satisfaction about the improvement on vision, six months after the surgery. However, there are still patients complaining that their vision performance did not achieve the expectation or was even worse than before surgery. The reasons causing the unexpected post-surgical outcome include undercorrection, overcorrection, induced HOA, and other postoperative diseases, most of which are caused by inaccurate ablation besides other pathological factors. Therefore, to find out the method to optimize the LASIK procedures and provide a higher surgical precision has become increasingly important. A proper method to calculate ablation profile and an effective way to control the laser beam size and shape are key aspects in this research to resolve the problem. Here in this Master of Philosophy degree thesis, the author has performed a meticulous study on the existing methods of ablation profile calculation and investigated the efficiency of wavefront only ablation by a computer simulation applying real patient data. Finally, the concept of a refractive surgery system with dynamical beam shaping function is sketched, which can theoretically overcome the disadvantages of traditional procedures with a finite laser beam size.

Stable multi-dimensional optical solitons have been predicted to exist in saturable instantaneous Kerr-like nonlinear systems for many years. The experimental observation of these objects is interesting scientifically and can have important applications. However, to date no experimental observation has been reported. The prospects of realizing these predicted phenomena depend on the accessibility of the nonlinear parameters in a physical feasible system. To address this question, we first develop a systematic way of determining the nonlinear properties of materials based on the previously developed spectrally-resolved two-beaming coupling measurement. This new method is used to measure the nonlinear properties of several materials. The results are used to assess the prospects of producing stable multi-dimensional optical solitons in saturable instantaneous Kerr-like nonlinear systems. We conclude that the prospects for producing three-dimensional solitons are poor. However, it is more likely to succeed in producing stable two-dimensional optical solitons.