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Biomimetic Model of Human Small Airway Monocyte and Macrophage Recruitment, Adaptation and Function
No full textBIOMIMETIC MODEL OF HUMAN SMALL AIRWAY MONOCYTE AND MACROPHAGE RECRUITMENT, ADAPTATION AND FUNCTION
Justin A. Hosten
165 Pages
Directed by Drs. Rabindra Tirouvanziam and Krishnendu Roy
Several muco-obstructive lung diseases in humans, including cystic fibrosis (CF), feature chronic recruitment of blood leukocytes and their reprogramming within the small-airway lumen, driving pathological adaptations such as dysregulated immune-mediator secretion and impaired bacterial killing. Most current studies focus on neutrophils or rely on in vivo / in vitro models that do not capture the nuances of the small airway.
To investigate these mechanisms, we engineered a biomimetic small-airway model in which primary human blood monocytes transmigrate across a human small-airway epithelium and, after 4-day exposure to macrophage colony-stimulating factor (M-CSF), differentiate into macrophages.
Airway-recruited monocytes (ArMos), generated using the control chemoattractant CCL2, underwent phenotypic, transcriptomic, and secretomic reprogramming upon transmigration and further changes upon differentiation into airway-recruited macrophages (ArMas), relative to circulating monocytes. Compared with non-transmigrated, M-CSF–differentiated macrophages, both ArMos and ArMas retained airway-associated features that are otherwise lost ex vivo. Conditioning with CF airway supernatant (cell- and bacteria-free sputum) produced additional, specific alterations in ArMos and ArMas across phenotype, transcriptome, and secretome compared with CCL2 conditions. Critically, CF ArMas (but not CF ArMos) showed a markedly reduced ability to kill Pseudomonas aeruginosa, a common CF pathogen.
These findings extend prior work on small-airway–recruited neutrophils and identify macrophage immune tolerance as one contributor to bacterial colonization in CF. Our biomimetic model supports further mechanistic and preclinical investigations of small-airway–recruited monocytes and macrophages in health and CF, as well as in other diseases featuring chronic airway inflammation and infection, such as non-CF bronchiectasis and chronic obstructive pulmonary disease (COPD)
Single-Cell Encapsulation of Non-Spore Forming Probiotic Bacteria for Increased Survivability Under Environmental Extremes
No full textSpore-forming bacterial cells possess extensive capabilities to survive extreme environmental conditions. The goal of this thesis is to explore the use of lipid-protein nanoparticles, extracted from the spore coats of a few distinct bacterial species, as a barrier and coating to protect probiotics from a range of distinct environmental pressures. Orally delivered probiotics must maintain a high viable cell count and be able to be stored for long periods without nutritional influx in order to be effective in humans and other animals.
I aim to understand how to characterize and manipulate the spore-based coating’s highly resistant, protective mechanisms for application across multiple families of beneficial bacteria to increase their survivability, both throughout the stress involved in manufacturing and conditions during digestion.
This research contributes to the foundational work for the improvement of oral probiotic viability, namely by producing multiple cross-order spore coated probiotics that have no sporulation mechanism themselves, and by showing the spore coat efficiently imparts its resiliencies on non-spore forming bacteria. In this work, I establish the ability for mechanically extruded spore coat nanoparticles (SCN) to be used for single-cell bacterial encapsulation of distantly related species. This protective layer increases their survivability under a wide range of physical extremes, including near boiling temperatures and acidic pH. I also show the ability for this coating and the cells’ biofilm to act as a filter for viral particles less than 150 nm in size. These characteristics are likely due to the spore coat’s function as a passive filter-like material, but I hypothesize this quality is reinforced with active spore coat proteins in the SCN.M.S.Biolog
Optimization of Drone and Truck Operations for Socially Optimal Disaster Relief
No full textIn post-disaster scenarios, the distribution of relief supplies is a complex process due to lacking the relief supplies and transportation means to completely and promptly satisfy survivors’ needs. The recent technological development of unmanned aerial technologies positions drones as potentially advantageous technology to support disaster relief distribution processes. Despite their limited capacity to carry goods, drones can access remote
areas and attain faster speeds than road vehicles typically used to deliver relief supplies. The study develops a mixed-integer non-linear model comprising the routing, location, and
allocation decisions for the distribution of relief supplies to survivors. The mathematical formulation minimizes a social cost function comprising logistic and suffering costs. The former costs are associated with trucks and drones transporting relief supplies and setting up points of distribution (PODs). The latter costs are associated with survivors’ mobility and deprivation. Supplies can be transported via multiple deliveries from distribution centers to PODs. Survivors have heterogeneous needs based on their vulnerability. Individuals who cannot walk to their preferred POD stay at their initial location and have the supplies delivered. Trucks can also carry drones to PODs, and drones can independently fly to the staying survivors. The formulation integrates multiple complex parts, such as the hybrid vehicle fleet, deprivation costs, and survivor mobility. This research contributes to disaster relief distribution operations by introducing a drone fleet to complement the traditional truck network, further prioritizing vulnerable survivors and reducing social costs.M.S.Mechanical Engineerin
A Methodology for the Selection and Integration of Self-Healing Architectures in Human Habitation Design
No full textFaults and degradations within human habitation systems can lead to rising costs, inefficiencies, and potential catastrophic failures of the systems in question. Earth based buildings consume a significant percentage of all energy worldwide, with a large component of this energy being wasted on faults and inefficiencies within heating and cooling systems. Deep space habitats have an inherent desire for increased resiliency due to the hostile environment they aim to protect human occupants from, with faults and degradations potentially jeopardizing missions, as well as the health and safety of occupants.
Self-healing systems are proving to be a very promising new approach in system design, particularly for their capability to introduce new layers of resiliency and efficiency into systems by the way of autonomy. This work aims to explore the applicability of self-healing systems into human habitation design, whether space focused or terrestrial, along with satisfying architectures for self-healing system implementation.
This thesis offers a method to integrate self-healing architectures within baseline systems during early phases of design, verify core system functionality, and quantify and compare benefits of self-healing architecture inclusion. Value of this methodology will be demonstrated on a simulated Mars surface habitat, with various self-healing architectures being selected and integrated within the system to show improved performance above baseline function
Systems Techniques for Enhancing Content Delivery in the face of Network Variability in the Edge-Cloud Continuum
No full textToday's internet-based applications involve end users, located at the edge of the network, communicating with services, often hosted in cloud data centers. Connecting the two ends is the wide area network. The last hop on the WAN, to the end user is termed the ``last mile'' of internet connectivity and spans a variety of technologies ranging from wired high-speed broadband to cellular networks, wireless ISPs, and community mesh networks. Of particular interest are the wireless means of last-mile connectivity, that exhibit temporal and spatial variability in the available capacity (bandwidth). This variable capacity is often the root cause of poor/variable user experience with applications like video conferencing, on-demand video streaming, and other bandwidth-intensive and/or latency-sensitive applications. Many application-specific solutions exist today, mainly meant for use with on-demand video streaming in wireless last mile cellular links, that may not generalize well across applications.
Most user-facing applications consist of client and server components, typically residing on user devices and cloud data centers respectively. Many solutions for deploying the server end of these applications have been developed with data center wired networks in mind. However, when we consider the space of community mesh networks, which, in addition to providing internet connectivity, often host local services such as file servers, caches, and video conferencing, existing techniques for application scheduling and orchestration for the server side components may not be a good fit since they often do not consider the effect of bandwidth variability.
In this dissertation, we take into consideration the variations in bandwidth inherent to wireless networks and design a holistic approach to the management of available bandwidth. We present three techniques for addressing bandwidth variations at different levels in the application ecosystem---at the level of user devices, at the level of an application service provider, and at the level of shared network infrastructure that hosts multiple applications. The techniques can be summarized as follows:
At the level of a mobile device, we demonstrate ways to manage the available bandwidth among multiple user applications by creating a system-wide bandwidth management service, to handle spatio-temporal variations in bandwidth, under conditions of user mobility.
From the perspective of an application service, or telecom provider, we consider the use of emerging technologies to effectively deliver content at the edge to mobile users, and at the same time, reduce reliance on cellular last mile data, using a combination of content prefetching and high speed out-of-band mmWave links.
At the level of shared network infrastructure, comprising multiple applications, we address the problem of scheduling applications in an environment where the communication links are predominantly wireless. We show the importance of bandwidth-aware scheduling and migration of application components on the performance of the application for a variety of applications.Ph.D.Computer Scienc
Hydrodynamic Stability of the boundary layer beneath a Stokes wave
No full textThis study aims to refine the linear stability analysis of the laminar boundary layer beneath a Stokes wave in deep waters, drawing on Fedele’s earlier findings. Fedele’s analysis focused on two-dimensional perturbations and employed a ”momentary” stability criterion. Here, we adopt a comprehensive approach by shifting to a full instability criterion, allowing for a more complete understanding of the stability characteristics of the boundary layer. Using Fourier and Chebyshev collocation methods to solve the Orr-Sommerfeld eigenvalue problem, we examine the stability of the flow across a broader parameter space. Our findings suggest that, while the laminar boundary layer remains stable for the momentary stability criterion against infinitesimal disturbances for all Reynolds numbers, the full instability criterion adopted here indicates that the flow may be linearly unstable. This full approach enables us to capture potentially unstable modes that may not be evident under a momentary instability framework. This work suggests that the recent experimental observations of spontaneous turbulence beneath unforced, non-breaking surface waves may be due to the instability of the boundary layer beneath the ocean wavesM.S.Civil Engineerin
Evaluating Induced Changes in Routing Behavior After the Implementation of the Northwest Corridor Managed Lane
No full textThis dissertation presents a methodology for evaluating the impact of the Northwest Corridor managed lane on total travel time and modelled route choice. The Northwest Corridor Express Lanes (NWC), completed in September 2018, added a total of 29.7 miles of barrier separated express lanes along I-75 from Akers Mill Road to Hickory Grove Road and along I-575 from I-75 to Sixes Road. The preponderance of research evaluates the effectiveness of managed lane implementations, primarily by computing the travel time savings between adjacent general-purpose lanes and express lanes under an assumed value of time. Few research studies examine differences in modelled route choice which are attributed to changes in total travel time from trip origin to trip destination after the implementation of a managed lane system which utilizes left turn exits and entries, while restricting access to general purpose lane exits along I-75 for Express Lane users. The fundamental difference between the NWC and other managed lane facilities is that the NWC have new dedicated access points which can only be traversed by Express Lane users. Drivers would enter and exit the managed lanes without crossing the general-purpose lanes and are forbidden from using these dedicated access points. The mandatory usage of left turn entries and exits to and from the Northwest Corridor managed lane may impact the total travel time experienced by motorists entering and exiting the managed lane particularly by impacting the distance traveled along arterial routes. A sensitivity analysis was conducted on toll rates charged per mile within a VISSIM® (version 9.0) traffic simulation to observe how modelled route choice is impacted after the implementation of the NWC, from trip origin to trip destination, from 5 A.M. to 11 A.M. The results of the VISSIM® simulations can be used to enhance the development of lane choice models, which do not currently handle managed lane systems which restrict access to general purpose lane exits. The traffic simulation, which includes 29.7 miles of the Northwest Corridor managed lane Corridor, 162 signalized intersections and approximately 38 centerline miles of Interstate, and over four hundred miles of arterial routes were used to model traffic flow from both Interstate and arterial routes to and from the managed lane. An Activity Based Travel Demand Model (ABM) provided by the Atlanta Regional Commission (ARC) is used to model trip entry and exit points for use within the traffic simulation. A sensitivity analysis on toll rates charged per mile was conducted within a VISSIM® simulation to examine the impact of the Northwest Corridor managed lane on total travel time and modelled route choice. Results from three case studies indicated that estimated travel time savings occurred most consistently along routes that contained only arterial and managed lane routes, where the travel distance from trip origin to the managed lane access point is less than two miles. Some queueing occurs in advance of managed lane exits under two conditions, namely when travel demands are high, and when the speed variations between leading and following vehicles are significant due to merging behavior near the managed lane access points. The research found that estimated travel time savings were most significant in cases when there is extreme congestion along arterial routes and the proximity to the managed lane entry from the trip origin is less than two miles away. There are differences in travel patterns associated with the addition of dedicated Express Lane ingress and egress access points, particularly at Roswell Road, where Express Lane users save up to thirteen minutes of travel time. The dissertation concludes with a summary of results, discussion on research limitations, some advice for practitioners, and recommendations for future research
Digital Wagers, Physical Pillars: Essays on Fintech, Banking and Small Businesses
No full textThis dissertation examines two distinct yet interconnected dimensions of the financial market, focusing on how emerging technologies and traditional structures shape investor behavior and business outcomes.
In the first chapter, we proxy retail investor attention through Google Trends and find that fungible and non-fungible crypto tokens generate greater attention from high–gambling propensity regions. Crypto attention is higher during bubble-like episodes in the crypto market and for more lottery-like tokens. Moreover, retail crypto attention decreases after sports gambling is legalized. Higher token attention is associated with more contributors and higher fundraising. However, consumer credit default rates spike after periods of high crypto attention, but solely in the subprime segment. Overall, our findings suggest that gambling preferences strongly predict retail investor interest in the crypto market.
In the second chapter, we examine how the physical presence of bank branches influences local small business performance. Using a novel dataset of merchant-level transactions, we exploit branch closures induced by bank mergers as an exogenous shock to local banking access. We find that losing local branches leads to significant declines in small business sales, fewer new entries, and higher exit rates; these adverse effects coincide with a reduction in local small business lending. The impact is especially pronounced for the smallest and most remote merchants, particularly in the retail and dining sectors. Areas with better internet connectivity experience milder effects, suggesting that digital banking and fintech services partly substitute for local branches. Notably, the decline in new business formation diminishes as branch networks recover, while the losses in sales and the increases in exits persist for longer. Our findings shed light on the significance of physical bank presence in gathering soft information and alleviating local small business lending friction.Ph.D.Managemen
Canonical mapping as a general purpose representation
No full textPerception is critical for robotic manipulation in open environments, where traditional approaches often produce task-specific predictions that are unsuitable for deformable objects or adaptation to other tasks. In this work, conducted within a USDA-funded initiative focused on automating the poultry processing industry, we propose canonical mapping as a near-universal and flexible object descriptor. Canonical mapping establishes correspondences between image pixels and a 3D mesh, enabling robust pose prediction for both rigid and deformable objects.M.S.Computer Scienc