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A Tale of Two Stromal Components: Influence of Fibroblasts, Innate Lymphoid Cells Type 2, and Interleukin 13 in Stomach Metaplasia
No full textA TALE OF TWO STROMAL COMPONENTS: INFLUENCE OF FIBROBLASTS, INNATE LYMPHOID CELLS TYPE 2, AND INTERLEUKIN 13 IN STOMACH METAPLASIA
Gastric cancer is one of the leading causes of cancer mortality worldwide, however, key regulators and mechanisms involved in gastric carcinogenesis remain unclear. The onset of metaplasia phenotypes in the stomach is correlated with the development of gastric cancer. Therefore, understanding the cellular events that lead to stomach metaplasia maturation and progression remains a priority. Studies from our group have demonstrated that immune components are key regulators for the development of metaplasia in the stomach. Moreover, increasing evidence suggests that fibroblasts can be responsible for the progression of pre-neoplastic lineages in different types of epithelial-type cancers. The first part of my studies shows the establishment and characterization of a novel organoid model for the study of Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) cells and demonstrates the role of Group 2 innate lymphoid cells (ILC2s) and Interleukin 13 (IL-13) in their maturation and proliferation. The second part of my studies shows the characterization of fibroblast populations across different stages of the stomach cancer carcinogenesis process and demonstrates the influence of metaplasia- and cancer-derived fibroblasts in metaplasia progression toward dysplasia
Framing "The Now" & "Present Moments" Which Lead to Flourishing on Navy Life
No full textDivinity School Doctor of Ministry in Integrative Chaplaincy Final ProjectsHypothesis: Do Navy members and their families face unique challenges to build and maintain a flourishing life compared to civilian families as their lives are ultimately undergirded by an institution whose ultimate mission is operational warfare?
This work considers theories, theology, and strategies for Navy members and their families to successfully adapt and overcome the unique lifestyles, transitions, and stressors associated with Navy life. The Japanese concept of “ikigai” is introduced as an inclusive model to characterize universal traits of life flourishing and meaning. Kairos theology is the transition point to frame the “present moment” and introduce Acceptance and Commitment Therapy. Theories of play and creativity demonstrate essential elements in understanding personal spirituality and flourishing. Haiku poetry is introduced as a simple, viable therapeutic tool for self-expression and grounding the in “present moment” leading to a transitional intersection towards a flourishing life for sailors and their families
Task-Based Design, Modeling, and Telemanipulation Assistance of Dexterous Robotics for Confined Spaces and Remote Intervention
No full textThe evolution from open surgery to laparoscopic surgery or minimally invasive surgery to robot-assisted minimally invasive surgery to the natural orifice and single port access surgery required more dexterous tools. The possible solutions to achieving such dexterity are using continuum robots and wire-actuated multi-articulated devices. As surgery
evolved from open to minimally invasive surgery (MIS), surgeons became challenged with perception barriers due to not holding the tools with their hands and the constrained visualization inherent to minimally invasive surgical access. Many robotic telesurgical systems in MIS have been developed to improve dexterity, hand-eye coordination, and sensation.
However, telemanipulation assistance for remote trauma care interventions is relatively unexplored. Moreover, the current paradigm of robot-assisted minimally invasive surgery lacks a set of systematic methodologies to quantitatively compare different manipulator designs and evaluate different kinematics configurations of the dexterous devices for robotic telesurgical systems. Such comparative approaches are important during the design stage for analyzing, characterizing, and making an informed decision between various design alternatives. This dissertation aims to address these challenges in the areas of design, modeling, and telemanipulation assistance. We first explore the feasibility of the identification of a robotic-palpation-assisted remote landmark (the cricothyroid membrane) for cricothyrotomy. Using a cricothyrotomy training simulator, we evaluated several telemanipulation alternatives for in-situ remote localization of the cricothyroid membrane through a small user study. The preliminary results show that the accuracy of remote landmark identification is improved when the user is aided with visual and force cues. Next, we address the challenge associated with the design and performance assessment of robotic telesurgical manipulators for operation in confined spaces. Unlike most works in the literature, we propose an approach for comparing design alternatives by considering the spurious motions along the length of the manipulator in lieu of existing approaches, looking at only the end-effector dexterity measures. We validate our proposed approach through two different illustrative simulation case studies. The dissertation further explores the design and performance assessment of continuum robots since they are increasingly becoming candidates for robotic architecture for surgical intervention. We present some geometrical insights for analyzing the kinematic singularity of continuum robots to improve the path planning and control of such dexterous devices. We also discuss the notion of safety zones around the nominal kinematic singular configurations to produce designs and paths that guarantee singularity-free performance despite norm-bounded deflections in configuration space. Lastly, we explore how force and motion transmission losses affect the minimal motion resolution at the end-effector of wire-actuated robots. We present a modeling framework that can be used at the design stage to evaluate the effects of internal transmission losses. Considerations of modeling the hysteresis effects of end-effector motion are used to define a performance measure that quantifies the quality of a given design within a workspace. We also discuss how multi-wire-driven wrists cannot be compared using conventional Jacobian-based performance measures because they disregard the wire-tension states. We discuss how to obtain the manipulability of multi-wire-driven wrists by manipulating conventional measures. The proposed methodology can guide the design of wire-actuated robots in selecting wire parameters, choosing wire arrangements, and determining their effects on the expected
uncertainty.
We believe the contributions presented in this dissertation have provided preliminary insights on the feasibility of robotic assistance for remote interventions and have provided design and modeling insights in the form of performance measures and geometric interpretations of singularities that can be used to guide the design and path planning of dexterous surgical devices
Modeling Vigilance State Effects on Functional Magnetic Resonance Imaging Data
No full textFunctional MRI is a non-invasive imaging modality that allows a researcher or clinician to quantify the activity in the brain that is associated with particular functions and behaviors based on region-specific blood-oxygen variations. Yet, as participants are in the MRI scanner, it has been found that many lose wakefulness within the first few minutes of the scan. The impact that naturally fluctuating levels of wakefulness (vigilance) have on fMRI data and on the outcomes of fMRI analyses have only recently gained attention in the field. Understanding how vigilance manifests in fMRI data may be essential since fatigue and disturbed sleep can be linked to disorders such as Epilepsy, Alzheimer’s Disease, mood disorders, traumatic brain injury, and more.
In this work, we aim to advance current knowledge of how vigilance fluctuations are expressed in fMRI data and build tools for modeling these state changes. In one avenue of work, we investigated a method that allows a measure of vigilance to be derived from previously collected fMRI datasets, so that future analyses can incorporate potential effects of (and information within) these state changes. The generalization of this tool was then evaluated across patient populations, data acquisition parameters, and processing methods, and was validated across several gold-standard vigilance measures.
The need to understand how effects of vigilance may relate to variability in fMRI data analyses has become increasingly important, particularly as the field has moved toward using functional MRI to characterize individuals rather than only population averages. Characterizing the role of vigilance could be key for developing neural biomarkers, as well as improving surgical outcomes, medication administration, or overall treatment in many different clinical populations
Matters of Trust
No full textMy dissertation offers a developmental account of trust which emphasizes trust’s contextual, embodied, and relational aspects. On my account, trust is a response to one’s situation that embraces risk and vulnerability. I argue that my developmental account is better suited for understanding how trust functions in applied contexts because it attends to trust as a necessary component of intimacy and as prerequisite for developing a practical identity.
I begin with a chapter that engages with Annette Baier’s work on trust. In this chapter I argue that what is typically cited from Baier’s work misrepresents her view and I draw attention to underappreciated features of her account. My reinterpretation of Baier forms the basis of my developmental account of trust, which is further developed in chapters four and five. In chapter two, I argue that an adequate account of trust must be able to: 1) account for distrust, 2) make a meaningful distinction between trust and reliance, and 3) attend to the way trust functions in relationships with asymmetries of power. Chapter three evaluates extant affective, doxastic, and ordinary language accounts of trust with respect to these requirements. I show that the existing accounts struggle to meet the third requirement and that the doxastic and affective accounts tend to fall prey to two pitfalls—the call to “demoralize” trust and the turn toward trustworthiness.
In chapter four, I argue that the developmental account of trust not only satisfies all three requirements better than the alternatives, but also that it does so in a way that avoids the pitfalls encountered by affective and doxastic accounts. This is because it possesses two key features: attention to social and historical context and an emphasis on relationships. I then show that how these two features pull the ethical value of trust into focus. In chapter five, I explore additional advantages of the developmental account. I demonstrate that one advantage is that it yields a more complete picture of how trust is impacted by the experience of trauma. I also show that attending to the lived, embodied experience of trust forges new paths for exploring the relationship between trust and the formation of identity. I conclude by arguing that the developmental account provides us with the conceptual resources that are necessary for understanding how trust can be fostered, maintained, and repaired in the real world
Ultra-Low-Overhead Arbitrary-Waveform Generation as a Circuit Macro: Augmenting the Characterization of Radiation-Induced Transient Effects in Highly Scaled Integrated Circuits
No full textArbitrary waveform generators (AWGs) are not typically feasible as subsystems on integrated circuits due to their size and complexity, but they are versatile circuits that are broadly useful. The purpose of this work is to show that by prioritizing minimal overhead and designing for targeted performance, as necessary for the application, it is possible to create a reusable on-chip AWG circuit macro in a small form factor. To support this claim, details and results are provided for a proof-of-concept implementation in a 45nm partially depleted silicon-on-insulator process. The presented design is able to achieve a small size by eliminating the complicated calibration and filtering circuitry commonly used in contemporary designs, instead relying on intrinsic accuracy of the base circuits. The reliability and accuracy of the AWG are driven by careful design down to the layout level, including the development of a variant of the traditional common-centroid layout technique called distributed-centroid layouts (DCL), which addresses the importance of bias circuitry in mitigating process-induced mismatch. A custom simulation workflow was developed to investigate the effectiveness of this technique at the circuit level as compared to other designs from the literature. The proof-of-concept circuit was designed to improve the characterization of radiation-induced transient effects in highly scaled integrated circuits by providing built-in self-test and hardware-emulation capabilities to a custom photocurrent measurement circuit (PMC). Details of this specific application are explored in detail, along with experimental measurements made using flash x-ray and pulsed laser sources. Alternative AWG designs that might benefit a broader application space beyond radiation effects are also provided
Ultra-Low-Overhead Arbitrary-Waveform Generation as a Circuit Macro: Augmenting the Characterization of Radiation-Induced Transient Effects in Highly Scaled Integrated Circuits
No full textArbitrary waveform generators (AWGs) are not typically feasible as subsystems on integrated circuits due to their size and complexity, but they are versatile circuits that are broadly useful. The purpose of this work is to show that by prioritizing minimal overhead and designing for targeted performance, as necessary for the application, it is possible to create a reusable on-chip AWG circuit macro in a small form factor. To support this claim, details and results are provided for a proof-of-concept implementation in a 45nm partially depleted silicon-on-insulator process. The presented design is able to achieve a small size by eliminating the complicated calibration and filtering circuitry commonly used in contemporary designs, instead relying on intrinsic accuracy of the base circuits. The reliability and accuracy of the AWG are driven by careful design down to the layout level, including the development of a variant of the traditional common-centroid layout technique called distributed-centroid layouts (DCL), which addresses the importance of bias circuitry in mitigating process-induced mismatch. A custom simulation workflow was developed to investigate the effectiveness of this technique at the circuit level as compared to other designs from the literature. The proof-of-concept circuit was designed to improve the characterization of radiation-induced transient effects in highly scaled integrated circuits by providing built-in self-test and hardware-emulation capabilities to a custom photocurrent measurement circuit (PMC). Details of this specific application are explored in detail, along with experimental measurements made using flash x-ray and pulsed laser sources. Alternative AWG designs that might benefit a broader application space beyond radiation effects are also provided
Helping the Suffering Move Toward Flourishing Spiritual Care Beyond Livable Disappointment and Common Unhappiness
No full textDivinity School Doctor of Ministry in Integrative Chaplaincy Final ProjectsThe places where chaplains perform ministry have them caring for suffering people. A common goal of psychiatry has been “to transform unbearable pain into livable disappointment”(Meador). Utilizing resources from philosophy, diverse religious and spiritual traditions, with particular emphasis on the author’s Judeo-Christian tradition, and positive psychology, the author seeks to help chaplains and other caregivers to equip suffering people to aspire for more than a livable disappointment to pursue a telos of human flourishing. Flourishing takes two forms, penultimate and ultimate. This project will take seriously the reality of pain and suffering and offer resources to pursue penultimate flourishing amid suffering and for those who desire, a path toward ultimate flourishing. Utilizing both inpatient and outpatient practices and group processes we will provide resources for well-being and ultimate flourishing
The Role of Immune Regulation In Host and Parasite Fitness
No full textInfectious diseases pose a continuous risk to the health and longevity of human, animal, and plant communities. Fortunately, immune systems are equipped to identify and eradicate these invading parasites. However, an effective immune response needs to balance the need to counteract a wide range of parasitic threats with the immunological and energetic costs associated with such defenses. This delicate balance is achieved through a layered network of immune regulators. These regulators ensure a swift and potent response to control infections, but they also promptly dial back the response to minimize immunopathology. Factors like life-stage, parasite exposure history, and genetic variability can influence how these regulators maintain this balance, but connecting the mechanisms driving changes to host-parasite interactions remains a challenge. Given these complexities, insects have emerged as an excellent model for studying immune regulation due to their well-defined immune networks and the ease of measuring their fitness traits. In the model insect Tribolium castaneum, exposure to a benign parasite early in life was found to influence immune regulation in adulthood. Using RNAi, it was also found that while amplifying immune pathway activation enhances immune responses and survival against bacterial infections, it exacts a significant cost on beetle fitness traits like female egg laying, gut health, body mass, and lifespan
