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SUMO2 Promotes Histone Pre-mRNA Processing by Stabilizing Histone Locus Body Interactions and Facilitating U7 snRNP Assembly
No full textHistone mRNAs are the only non-polyadenylated mRNAs in eukaryotic cells and require specialized processing in the histone locus body (HLB), a nuclear body where essential processing factors, including the U7 snRNP, are concentrated. Recent studies have revealed that misregulation of histone pre-mRNA processing can lead to polyadenylation of histone mRNAs and disruption of histone protein homeostasis. Despite links to human disease, the factors contributing to polyadenylation of histone mRNAs and the mechanisms underlying HLB assembly and U7 snRNP biogenesis remain unclear. Here, we report novel functions of the small ubiquitin-related modifier 2 (SUMO2) in promoting histone pre-mRNA processing. Using a SUMO2 knockout osteosarcoma cell line, we identified a defect in 3’ end cleavage and a global increase in histone mRNA polyadenylation. Subsequent analysis of HLBs revealed increased dynamics and reduced levels of the U7 snRNP complex. By over-expressing U7 snRNP-specific components, Lsm11 and U7 snRNA, we rescued U7 snRNP levels and processing defects in SUMO2 knockout cells. Through analysis of Lsm11, we identified a SUMO-interacting motif in its N-terminus required for efficient formation of U7 snRNP. Collectively, we demonstrate that SUMO2 promotes histone pre-mRNA 3’ end processing by stabilizing HLB interactions and facilitating U7 snRNP assembly
DEVELOPMENT OF LANDING MODULE IN NOVEL STACKABLE UNMANNED AIRCRAFT SYSTEM & TESTING OF CUSTOMIZABLE SOFT ACTUATOR
No full textUAS:
Unmanned Aerial Vehicles (UAVs) have experienced significant growth over the past decade, with over 1.78 million small recreational Unmanned Aircraft Systems (UAS) registered in the United States by 2023 and a projected annual increase of 3.7% [1]. A typical UAS comprises at least one UAV, a ground control station, and mission-specific payloads, enabling centralized monitoring and coordination of multiple aerial platforms [2]. Despite this growth, there are currently no commercially available, portable, multi-drone UAS packages that balance compactness, usability, and functionality. This work presents a proof of concept for a compact, retractable landing module designed for Vertical Take-Off and Landing (VTOL) drones and integrated into a portable UAS control tower. The landing module features actuated retractable landing pads capable of rapid deployment, ArUco markers to assist with precision landing, and a structurally optimized framework informed by topology optimization techniques. Design decisions were guided by academic literature and market research. Ongoing work includes further design iterations and isolated validation of key components to maximize the robustness and usability of the final product.
Soft Robot:
Soft robotics has promising applications due to its inherent compliance, adaptability, and gentle interaction with sensitive environments. However, modelling of soft actuator motion remains challenging due to non-linear behaviors and material complexities. This work contributes to the broader goal of developing a bio-inspired hydraulically actuated soft robotic pectoral fin for enhanced maneuverability and control in underwater vehicles [3]. Specifically, this thesis focuses on the development, testing, and validation of a linkage mechanism designed to facilitate accurate benchmarking of a computer vision-based visual tracking algorithm. The objective is to validate key performance metrics such as positional accuracy and reliability of the algorithm for tracking soft robot movement. Subsequent experimental procedures will involve repeated systematic variation of actuator pressures and motion trajectories to develop software capable of predicting soft robot movement based on pressure input. Results will provide insights into the practical deployment of bio-inspired soft actuators in underwater applications, highlighting both their advantages and current limitations
Vorticity dynamics in flows over bluff bodies
No full textThis thesis presents a numerical study of the vorticity dynamics in the boundary layer separation and vortical structures of bluff body flows.
A finite-volume based incompressible flow solver on three-dimensional curvilinear multiblock grids is implemented with large-scale parallelization. The solver is rigorously validated against reference simulations and experimental measurements, ensuring its reliability for capturing boundary layer dynamics and turbulent vortical structures.
A back-in-time analysis is first performed to find the origins of vorticity in boundary-layer separations and vortex shedding. Using the adjoint-vorticity framework, the vorticity in these structures are traced back to earlier time interior vorticity and wall vorticity fluxes. For flow over a sphere at Re=200, axisymmetric two-dimensional separation is shown to arise from wall fluxes, with a contribution from downstream of separation that is absent from classical description by Lighthill. At Re=300, the formation of hairpin vortices in the wake is quantitatively linked to the tilting of azimuthal vorticity on the sphere surface. For a prolate spheroid at Re=3000, the three-dimensional separation reveals a tilting-driven migration of vorticity contributions, contrasting with two-dimensional separation. Additionally, the origins of primary and necklace vortices in the spheroid wake are traced to surface interactions.
Building upon the aforementioned study, the second part investigates the connection between drag force and vorticity dynamics through the Josephson-Anderson relation. The drag force arises from the vorticity flux across streamlines of a potential flow. This flux is further analyzed using the Huggins vorticity flux tensor. For flow over a sphere at Re=200, drag force is attributed to viscous wall vorticity flux and shear layer advection. At Re=3700, turbulent transport enhances wake vorticity redistribution, driving the enthalpy recovery. For a prolate spheroid at Re=3000 and 20 degree incidence, drag is primarily linked to boundary-layer vorticity transport, with opposing effects from primary and secondary separation, the latter explained through a proposed vortex-induced mechanism.
Build upon the classical theory of bluff body flows and the modern development of vorticity theory, the thesis provides novel interpretation for boundary layer separation and drag force from the perspective of vorticity dynamics
Economic sanctions, reciprocity, and retaliation: exploring how states adapt and cope with sanctions
No full textDespite the widespread use of sanctions as a foreign policy tool, the responses of sanctioned states towards sanctioning states vary. In response to Western sanctions over Russia’s invasion of Ukraine, Russia imposed export restrictions and temporarily cut off natural gas supplies. North Korea, rather than resorting to reciprocal economic measures, opted for different forms of retaliation, such as cyber-attacks. Meanwhile, some countries did not impose any meaningful countermeasures even when subjected to substantial pressure through sanctions. My research aims to address two key questions: (1) Why do some sanctioned states retaliate against sanctioning states while others do not? (2) If they do so, how do their countermeasures differ from country to country?
To answer these questions, my research employs a mixed-method research design. I use cross-national statistical analysis examining 320 sanction episodes imposed by the United States and European Union and conduct country case studies of Russia (economic retaliation), North Korea (non-economic retaliation), and Myanmar (no retaliation). I find that political regimes in the sanctioned state shape whether and how they retaliate. Authoritarian regimes are more likely to retaliate, and regimes that are dependent on the military are less likely to retaliate. This research contributes to the literature on reciprocity and helps in formulating more effective sanctions policies by understanding the drivers and patterns of sanctioned countries’ retaliatory acts
Active transport phenomena in biology across different scales
Get PDFBiological systems function within an aqueous environment enriched with various solutes, including ions and proteins. The transport of these essential components—water and solutes—is an active process that operates across multiple scales, from single cells to multicellular structures and systemic circulation. Active transport plays a crucial role in cellular metabolism, growth, migration, morphogenesis, and systemic functions such as blood circulation. While many studies focus on transport driven by single environmental factors, such as hydrostatic pressure, it remains unclear how cells integrate multiple stimuli, including hydrostatic and osmotic pressures, to regulate active transport. Additionally, the interplay between transport processes across scales remains poorly understood, particularly in establishing stable metabolic activity and maintaining thermodynamic gradients out of equilibrium. In this thesis, we first provide a general framework for understanding active transport in biological systems, focusing on solute and water transport across different scales. For solute transport, we examine how the active intracellular transport of macromolecules, such as proteins, contributes to stable cell growth and nuclear size scaling. We then explore the coupling between solute and water transport, demonstrating how cells regulate their fluid environment by modulating membrane tension and ion transporter distribution. This regulation enables directed migration at both the single-cell and collective-cell levels. On a systemic scale, we investigate the role of active fluid pumping by renal epithelial and endothelial cells in maintaining sustained pressure and osmolarity gradients, which are essential for stable blood circulation in the human body. Finally, we discuss emergent behaviors driven by active transport in multicellular systems, using immune cell pattern formation as an example. Our work establishes a theoretical framework for understanding active transport in biological processes, providing new insights into cell migration, morphogenesis, and systemic fluid regulation
Data-driven Multi-Scale Modeling with Uncertainty Quantification of Damage in Unidirectional and Woven Composites Using Parametrically-Upscaled Continuum Damage Mechanics (PUCDM) Model
No full textThis dissertation develops a multiscale framework utilizing 2-level parametrically-upscaled continuum damage mechanics (PUCDM) models to predict damage evolution in unidirectional and plain weave woven composites. The 2-level PUCDM models, viz. PUCDM-1 and PUCDM-2, bridge three levels (micro, meso, and macro) of the composite hierarchy. The functional forms of the constitutive coefficients in the PUCDM-1 and PUCDM-2 models, in terms of representative aggregated micro- and meso-structural parameters (RAMPs), material properties, and damage-induced dissipation energy, are derived by machine learning methods.
The PUCDM-1 model is derived with uncertainty quantification for unidirectional composites to account for the microstructure characteristic model reduction error, the neural network-based model reduction error, and aleatoric uncertainty due to inherent microstructural variability through uncertainty propagation. Bayesian principal component analysis (BPCA) is utilized to derive probabilistic, microstructure-dependent constitutive parameters in the PUCDM model. A Taylor expansion-based uncertainty propagation method enables computationally efficient, time-integration of the stochastic material response with consideration of uncertainty in the RAMPs.
With the level-1 PUCDM model integrated as the constitutive model for fiber yarns, the level-2 PUCDM model (PUCDM-2) is developed by upscaling the deformation and damage responses of the mesoscopic woven RVEs, manifesting the effects of damage in fiber yarns and the surrounding matrix, as well as the fiber yarn-matrix interfacial debonding. Coefficients in the level-1 and 2 PUCDM models are represented as functions of key RAMPs extracted from the underlying RVEs. The resulting two-level PUCDM models integrate damage mechanisms and morphology descriptors across different length scales. Both PUCDM-1 and PUCDM-2 can be readily implemented in any finite element code like ABAQUS through user-interface windows for efficient damage analysis at the structural scale (hierarchical level-3).
The PUCDM-1 and PUCDM-2 model effectiveness are validated through comparisons with numerical results and experimental data, demonstrating their robust performance and accuracy in predicting complex composite damage behavior at multiple scales. The validated PUCDM model is then applied to analyze damage mechanisms in single-edge notched bending (SENB) tests on woven composite beams. Parametric studies are performed to investigate the effect of lower-scale morphology and material properties on the structural damage response of the beams. The two-level PUCDM models are capable of predicting stress-strain and damage evolution with high computational efficiency and accuracy
Investigating DNA Polymerase Alpha in the C. elegans germline
Get PDFUnderstanding the mechanisms behind adult stem cell maintenance and division is an important effort in medicine for developing treatments for a multitude of illnesses. Asymmetric stem cell division offers many insights on how stem cells can maintain their potency while still providing cellular division to aid in regeneration and repair of damaged tissue. Applying asymmetric stem cell mechanisms to symmetrically diving systems may offer a way to genetically induce maintained potency when there normally wouldn’t be. In this study, our goal is to induce stemness—a phenomenon observed in Drosophila melanogaster via heterozygous mutations in lagging-strand DNA polymerase α (Polα) or through a small-molecule Polα inhibitor—in the symmetrically dividing germline stem cell population of Caenorhabditis elegans. We accomplish this by introducing a heterozygous deletion for DNA Polymerase Alpha (POLA-1) in order to create delayed lagging strand synthesis during stem cell replication. We find that genetically reducing the levels of POLA-1 via the heterozygous deletion result in sustained germline stem cell maintenance in physiological conditions such as aging and pathological conditions such as an increased resistance to acute pathogen infection. Furthermore, we demonstrate that significant effects of reducing POLA-1 are dependent on the homeostasis of the worm
DEVELOPING A BINATIONAL CLIMATE ADAPTATION AND RESILIENCE PLAN FOR THE SHARED WASTEWATER SYSTEM
Get PDFWater and wastewater management provide essential services that are often taken for granted or overlooked. However, system failures, compounded by climate change impacts, can have cascading impacts on public health and the environment. The shared wastewater system between the bordering cities of San Diego and Tijuana highlights the unique challenges of transboundary wastewater management, exacerbated by aging infrastructure and climate change. This study applies a systematic and mixed-methods approach to assess the climate vulnerabilities of key wastewater facilities across the San Diego and Tijuana region under future climate scenarios. A prescriptive climate adaptation planning and assessment framework was utilized to evaluate and identify the key components to develop a binational climate adaptation and resilience plan tailored for the sector and region. The findings underscore the urgent need for coordinated binational adaptation planning, prioritization of infrastructure upgrades, and sustained stakeholder collaboration from both countries to safeguard public health, protect environmental quality, and build a more resilient wastewater management system
Compact and Automated Multi-solution Controller for Microfluidic Devices
Get PDFMicrofluidic devices have been increasingly used for point-of-care (POC) applications like medical diagnosis. However, current microfluidic POC devices are only compatible with small sample volumes and low flow rates. Assays that require a large volume of sample or a high flow rate still rely on bulky and expensive infrastructures. Here, we demonstrate a compact and automated multi-solution controller for microfluidic devices compatible with high flow rates. The controller requires only 0.5 square feet of workbench space, and the total cost to build is approximately $ 487.94. It can control the pressure on multiple solutions to complete a series of procedures automatically. The controlled pressure ranges from 0 to 50 psi , making it suitable for a wide range of applications of microfluidic devices. We believe that the multi-solution controller can significantly reduce the cost and simplify the process for flow control for microfluidic devices
CAN INVASIVES ACT AS UNEXPECTED GOOD? A REVIEW OF PHRAGMITES AUSTRALIS’ IMPACT ON NORTH AMERICAN WETLAND CARBON DYNAMICS
Get PDFWetland ecosystems are complex ecosystems that are invaluable due to the various environmental functions they perform and services they provide at the population, ecosystem, and biosphere level. As the climate crisis intensifies, the role of wetlands as a carbon sink is becoming more essential now than ever. For this reason, the protection of wetland ecosystems from threats such as degradation via alien species invasion is of utmost importance. Common reed (Phragmites australis australis) is one of the most found invaders in North American wetland ecosystems. The purpose of this study is to address the following questions regarding P. australis: (1) What impacts does the presence of P. australis have on wetland carbon sequestration and storage? (2) Do these grasses provide some net benefits to wetland ecosystem carbon cycling in the face of climate change? and (3) What implications do these findings have on wetlands management in terms of P. australis removal efforts? To answer these questions a literature review utilizing peer reviewed studies on P. australis invasions in North America are selected, compiled, and screened. According to articles compiled through the database search, there is not currently a consensus on the best proceedings for Phragmites management in terms of impact on carbon cycling. Even though P. australis alters native wetland ecosystems and the organisms inhabiting them, yielded results display the species has the capacity to benefit society due to their ability to positively influence wetland carbon dynamics