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DEVELOPING SHAPE-CHANGING MECHANISMS FOR INJECTABLE SOFT-GEL MICRONEEDLES IN THE GASTROINTESTINAL TRACT FOR ORAL DRUG DELIVERY
No full textHydrogel microneedles (MN) have been largely explored for transdermal applications, from sustained drug release and diagnostics to cosmetic patches. Hydrogels exhibit tunable swelling and flexibility, and in some cases biocompatibility, which make them useful for a variety of medical applications. In particular, superabsorbent particles represent a specific type of hydrogel that exhibits rapid, high volume expansion. In this work, we hypothesize that the exploitation of biocompatible hydrogel swelling can enact pain-free soft-gel microneedle drug delivery in the gastrointestinal tract. We developed and characterized two mechanisms of MN injection: hydrogel bilayer swelling/unfolding and rapid superabsorbent particle expansion. We used rheological testing to characterize the mechanical properties of gelatin needles and developed an agarose intestinal phantom for in vitro experiments. Future work will explore in vivo and ex vivo microneedle performance, swelling prediction studies, and microneedle strength optimization
ANALYZING EPIDEMIC SPREAD AND EMOTION CONTAGION WITH AGENT-BASED SIMULATION AND SYSTEM DYNAMIC MODELING
Get PDFThis paper introduces an innovative model developed through Agent-Based Model (ABM), which have become crucial in predicting public policy outcomes, particularly observed during the last three years of the COVID-19 pandemic. Our model is designed to analyze the impact of masking wearing behaviors and large-scale evacuations, focusing on a large university campus and its nearby areas. To facilitate this, we integrated a dashboard for enhanced analysis, allowing for easy visualization and comparison across different simulation parameter settings. A key addition to our model is the integration of agents' emotion, inspired by observations of mask-wearing behaviors. This module adds a new layer of complexity by modeling how external factors influence agents' behaviors and subsequent actions. The paper specifically explores the simulator's ability to reflect the impact of various masking policies during an earthquake evacuation scenario, intertwining this with the dynamics of the emotional model. This comprehensive approach not only examines the direct effects of these policies but also delves into the more subtle nuances of agent behavior under such circumstances. It is a powerful tool that can provide accurate recommendations of pandemic management for policy makers
ASYNCHRONOUS ONLINE LEARNING: ITS IMPACT ON LEARNERS IN HIGHER EDUCATION
Get PDFThis dissertation explores the impact that asynchronous online learning has on learners in higher education. Through a mixed-methods approach, this study investigates a learner’s sense of belongingness, their level of participation and their perceptions in online learning communities. The findings of this research revealed that participants enrolled in asynchronous online courses lacked a sense of belongingness. Additionally, the findings revealed that the learners were not actively engaging with peers in their online courses. However, the findings also revealed that the online learners in asynchronous environments would enjoy settings that facilitated more opportunities for peer-to-peer engagement. This research contributes to the field of Higher Education by providing insights that will contribute to student retention rates, and more stable enrollment numbers at various institutions
Fairness in Machine Learning Methods for Surgical Skill Assessment
Get PDFSurgical skill development is crucial for ensuring high-quality patient care and successful surgical outcomes. Traditional methods of surgical skill assessment, such as direct observation and outcome-based metrics, often suffer from subjectivity and scalability issues. Video-based assessments (VBA) using machine learning (ML) could be a promising alternative, offering the potential for more objective and scalable evaluations. However, a significant challenge in deploying ML models in this context is the potential for bias, which can stem from various sources, including the data. Such biases can skew results, leading to unfair assessments and potentially impacting surgeon careers and patient outcomes.
Utilizing a pairwise comparison framework, we introduce bias of various intensities at a granular level and quantify it. Our findings highlight a significant difference in model evaluation on biased test sets, with an average 8% to 17.1% drop in Area Under the Curve (AUC) scores for each 10% increase in rater bias. We also simulate realistic ratings for a sample of raters based on a study’s data on IAT scores of 131 surgeons, ensuring that the simulated data reflects the variability and distribution seen in real-world data.
Next, we evaluate the performance of models trained on biased and unbiased data sets, demonstrating that models trained on unbiased data outperform biased models in this case. We also propose a pipeline that begins with the quantification of dataset bias, which could be used to train models that compensate for identified biases downstream through reweighting and other corrective techniques. Central to our method is the use of fairness metrics, such as the true positive rate (TPR) and false positive rate (FPR) for equalized odds, to measure bias. These metrics are calculated by comparing rater labels against expert labels within strategically sampled subsets of the data.
Our work underscores the necessity of addressing implicit bias in training and test sets to ensure the fairness and reliability of automated surgical skill assessment models
Dynamic Simulation and Modelling for Continuum Load of Robotics Impedance Control
Get PDFTranscranial magnetic stimulation (TMS), a safe neuro-modulation technique based on electromagnetic induction of an electric field inside the brain, has shown behavioral effects and therapeutic potential. Applying robots to the TMS procedure is shown to improve stability and consistency. However, unlike human operators, robots can hardly detect the contact force if the attached device is a varying load and if the sensor is not directly placed at the contact region. This limitation adversely affects the safety of the TMS therapy. Impedance Control could potentially address this problem by considering the contact force as impedance and changing the robots' motion accordingly. The impedance controller requires accurate measurement of the contact force, but, with the TMS cable attached, the contact force is highly coupled with the gravitational force of the cable.
This thesis presents novel approaches to tracking or simulating the continuum load of the cable during robotic TMS, making the decoupling of the contact force and the load possible. The kinematics-based modeling approach and dynamic modeling approach, employing real-time integration of Taichi physics engine to ROS and a novel marker labeling algorithm, provide comprehensive and robust solutions to the challenges of accurate and precise external force estimation. The proposed kinematics-based method is tested in realistic experiments by projecting the reconstructed object onto the image captured by an RGBD camera, and the computational demand of the dynamics-based method is examined in the simulation environment. The positional error of the TMS coil localization in the simulation is evaluated by applying artificial external loads to the robot. This thesis shows that the proposed modeling approach improves the performance of the impedance control applied for Robotic TMS therapy in the presence of continuum loads, which paves the way for real-time integration of force control and robotic TMS therapy
Development and Evaluation of Control Methods with Dynamic RCM Constraint on Surgical Robotics System in Minimally Invasive Surgery
Get PDFMinimally Invasive Surgery (MIS) has significantly enhanced surgical outcomes for both surgeons and patients compared to traditional open surgery. Surgical robotics plays a important role in MIS, enabling precision and minimally invasive procedures previously unattainable. Remote Center of Motion (RCM) is important to the effectiveness of surgical robotics, which ensures precise tool movement and minimizes trauma. RCM can be static or dynamic, tailored to specific application. Numerous studies have explored RCM implementation, including mechanical designs and control algorithms. Smart Tissue Autonomous Robot (STAR) is a surgical robotics system. However, due to its unique mechanical structure, existing RCM control algorithms cannot be directly applied to STAR. This study introduces two control methods for STAR based on position control and velocity control. These methods are crafted to make use of the Degree of Freedom (DoF) near the tool tip. Experimental validation using the MATLAB Robotics System Toolbox demonstrates the superiority of the position control algorithm for STAR operations. A C++ package is developed, compatible with both ROS 1 and ROS 2 frameworks, to implement the chosen algorithm. Simulation in Gazebo and RViz further confirms the algorithm's effectiveness in a controlled setting
Mecom and brain vascular angiogenesis in Alzheimer's Disease
No full textAlzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological changes, including the deposition of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Emerging evidence suggests that cerebrovascular dysfunction and angiogenesis play crucial roles in AD pathogenesis. Mecom, a transcriptional regulator associated with venule endothelial cells (vEndo), has been implicated in AD and shown to be upregulated in AD brain vasculature. To elucidate the role of Mecom in AD-related angiogenesis, we conducted a comprehensive analysis using immunohistochemistry staining in post-mortem AD brain samples. Our results revealed a significant increase in Mecom expression levels in the vascular endothelial cells of AD patients compared to controls, with a progressive elevation correlating with disease severity. Furthermore, utilizing in vivo and in vitro models, we investigated the impact of Mecom dysregulation on angiogenesis dynamics and endothelial cell function. Our findings demonstrate that Mecom overexpression could promote aberrant angiogenesis and disrupt endothelial cell integrity, suggesting a potential mechanistic link between Mecom dysregulation and cerebrovascular dysfunction in AD. Overall, our study sheds light on the role of Mecom in AD-related angiogenesis and provides valuable insights into the underlying mechanisms driving cerebrovascular alterations in AD pathogenesis. These findings may offer novel therapeutic targets for the treatment of AD-associated cerebrovascular dysfunction and cognitive impairmen
COUNTERFACTUALITY, NECESSITY AND POSSIBILITY IN TRUTHMAKER SEMANTICS
Get PDFTruthmaker semantics is a formal system of linguistic meaning, recently developed by Kit Fine and Stephen Yablo. Fine and Yablo argue that it provides novel and interesting solutions to various outstanding issues faced by alternative frameworks of linguistic meaning, most notably the possible-worlds framework. The possible-worlds framework is originally developed to solve the problems faced by the earlier truth-functional treatments of language such as Ludwig Wittgenstein’s. The possible-worlds framework was especially successful in modeling modals and conditionals. This dissertation focuses on modals and conditionals, but from the perspective of truthmaker semantics. The general theme consists in exploring issues stemming from the possible-worlds treatment of modals and conditionals, especially counterfactuals such as “If it had rained, the party would have been cancelled”, necessity claims such as “It must have rained yesterday” and possibility claims such as “It might have rained yesterday”. Chapter 1 argues that the logic of counterfactuals as validated by the possible-worlds models developed by David Lewis and Robert Stalnaker makes counterintuitive predictions due to their permission to substitute the antecedent of any counterfactual with a logically equivalent antecedent. I show the truthmaker semantics can make the right predictions for the cases to be discussed. Chapter 2 takes on one of the oldest puzzles about epistemic necessity. The literature reached a stalemate about the logical strength of the epistemic modals such as “It must be raining”. Some argued “It must have rained” entails “It rained” and some argued it does not. I argue this is a false dilemma by disambiguating the sense of entailment involved in the debate. Truthmaker semantics naturally gives rise to many different senses of entailment. I demonstrate that the sense of entailment for epistemic necessity arises from a different sense of entailment than the lack thereof. Chapter 3 focuses on possibilities. Philosophers and logicians often talk about possibilities as if they could be reduced to possible worlds, situations or states of affairs. However, looking at the behavior of possibility-denoting expressions such as the possibility that it is raining outside right now in extensional environments tell a different story. In particular, possibilities cannot be reduced to possible entities, be it worlds, situations or states of affairs. I argue that there are independent principles in truthmaker semantics which drive us to this conclusion independently and force us to postulate possibilities as entities of their own kind. I provide an interpre- tation of these irreducible possibilities by relying on evidence from cognitive science as well
Modulating Oxygen and Reactive Oxygen Species Signaling in Bone Tissue Engineering: From a Theoretical Framework to Scaffold Development
No full textThis research underlines the complex roles of oxygen (O2) and reactive oxygen species (ROS) in bone tissue engineering, and their critical involvement in bone regeneration. Oxygen-generating scaffolds (OGS) have been developed to enhance healing processes, signaling an evolving field. To achieve next-generation OGS designs, not only should the material design be tailored to the O2 demand in bone defects, potential integration of image-based O2 monitoring systems to access the real-time O2 demand and machine learning methods for predicting OGS efficacy could all enhance OGS development. With the goal of advancing current OGS, we identified quercetin, a natural antioxidant, to mitigate the inadvertent increase in ROS during O2 release in calcium peroxide scaffolds. These investigations extend into the cellular impacts of hypoxia and quercetin, studying how they affect stem cell behavior, including ROS levels, proliferation, and osteogenic differentiation. The findings offer valuable insights into the delicate balance required between promoting regenerative oxygenation and managing oxidative stress, with the eventual goal of optimizing scaffold designs for superior clinical outcomes in bone repair. This work lays the groundwork for a more nuanced approach to bone scaffold engineering, where the modulation of O2 and ROS is precisely controlled to support the intricate requirements of bone healing
Rab30 facilitates lipid homeostasis during fasting
Get PDFIn order to facilitate inter-tissue communication and exchange of proteins, lipoproteins, and metabolites with the circulation, hepatocytes rely upon an intricate and efficient intracellular trafficking system regulated by small Rab GTPases. Despite the importance of Rab GTPases in regulating intracellular trafficking, the physiological roles of many Rabs in mammalian tissues remain uncharacterized. For example, while there are intriguing associations between the Golgi-localized Rab30 and liver metabolism, its precise function is enigmatic.
We have identified that Rab30 expression is amplified in liver-specific knockout mice of hepatic β-oxidation via carnitine palmitoyltransferase 2 (Cpt2L-/-), which exhibit fasting-induced fatty livers, serum dyslipidemia, and heightened peroxisome proliferator activated receptor alpha (Pparα) transcriptional activity.
We therefore hypothesized that Rab30 plays a role in liver lipid metabolism. In this work, we show that Rab30 is specifically regulated during fasting by Pparα in hepatocytes. Live-cell super-resolution imaging and biochemical in vivo proximity labeling demonstrates that Rab30-marked vesicles are highly dynamic and interact with proteins at the Golgi apparatus and throughout the secretory pathway. Rab30 whole-body, liver-specific, and Rab30;Cpt2 liver-specific double knockout (DKO) mice are viable and display intact Golgi ultrastructure. However, the loss of Rab30 in Rab30;Cpt2 DKO mice suppresses serum dyslipidemia observed in Cpt2L-/- single knockout mice. Corresponding with decreased serum triglyceride and cholesterol levels, Rab30;Cpt2 DKO mice exhibit decreased circulating but not hepatic ApoA4 mRNA and protein. Additionally, proteomics shows secreted proteins are retained in the livers of DKO mice, indicative of a trafficking defect. Our data reveals that, while liver Rab30 expression is dispensable for the fasting response, Rab30 plays a supporting role in the trafficking of hepatic proteins and lipids in the face of nutrient deprivation