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- Title
- Probing the Influence of Cx43 and Glucose on Endothelial Biomechanics.
- Creator
-
Islam, Md Mydul, Steward, Robert, Kassab, Alain, Mansy, Hansen, Willenberg, Bradley, University of Central Florida
- Abstract / Description
-
Endothelial cells (ECs) form the innermost layer of all vasculature and constantly receive both biochemical and biomechanical signals, yielding a plethora of biomechanical responses. In response to various biochemical or biomechanical cues, ECs have been documented to generate biomechanical responses such as tractions and intercellular stresses between the cell and substrate and between adjacent cells in a confluent monolayer, respectively. Thus far, the ability of endothelial tight junctions...
Show moreEndothelial cells (ECs) form the innermost layer of all vasculature and constantly receive both biochemical and biomechanical signals, yielding a plethora of biomechanical responses. In response to various biochemical or biomechanical cues, ECs have been documented to generate biomechanical responses such as tractions and intercellular stresses between the cell and substrate and between adjacent cells in a confluent monolayer, respectively. Thus far, the ability of endothelial tight junctions and adherens junctions to transmit intercellular stresses has been actively investigated, but the role of gap junctions is currently unknown. In addition, there is no report of the independent influence of hyperglycemia on endothelial biomechanics present in the literature. To fill these gaps, we conducted a two-fold study where we investigated the influence of endothelial gap junction Cx43 and hyperglycemia in endothelial tractions and intercellular stress generation. In the first study, we selectively disrupted and enhanced EC gap junction Cx43 by using 2',5'-dihydroxychalcone and retinoic acid, respectively and in the second study, we cultured ECs in both normal glucose and hyperglycemic condition for 10 days. In both studies, tractions and intercellular stresses were calculated using traction force microscopy (TFM) and monolayer stress microscopy (MSM), respectively. Our results reveal that Cx43 downregulation increased as well as decreased endothelial avg. normal intercellular stresses in response to a low (0.83 (&)#181;M) and a high dose (8.3 (&)#181;M) chalcone treatment, respectively, while Cx43 upregulation decreases avg. normal intercellular stresses in both treatment conditions (2.5 (&)#181;M and 25 (&)#181;M) compared to control. In addition, we observed a decrease in intercellular stresses with hyperglycemic condition compared to control. The results we present here represent, for the first time, detailed and comprehensive biomechanical analysis of endothelial cells under the influence of glucose and the gap junction Cx43. We believe our results will provide valuable insights into endothelial permeability, barrier strength as well as leading to a greater understanding of overall endothelial mechanics.
Show less - Date Issued
- 2019
- Identifier
- CFE0007819, ucf:52805
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007819
- Title
- IMPROVING AIRLINE SCHEDULE RELIABILITY USING A STRATEGIC MULTI-OBJECTIVE RUNWAY SLOT ASSIGNMENT SEARCH HEURISTIC.
- Creator
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Hafner, Florian, Sepulveda, Alejandro, University of Central Florida
- Abstract / Description
-
Improving the predictability of airline schedules in the National Airspace System (NAS) has been a constant endeavor, particularly as system delays grow with ever-increasing demand. Airline schedules need to be resistant to perturbations in the system including Ground Delay Programs (GDPs) and inclement weather. The strategic search heuristic proposed in this dissertation significantly improves airline schedule reliability by assigning airport departure and arrival slots to each flight in the...
Show moreImproving the predictability of airline schedules in the National Airspace System (NAS) has been a constant endeavor, particularly as system delays grow with ever-increasing demand. Airline schedules need to be resistant to perturbations in the system including Ground Delay Programs (GDPs) and inclement weather. The strategic search heuristic proposed in this dissertation significantly improves airline schedule reliability by assigning airport departure and arrival slots to each flight in the schedule across a network of airports. This is performed using a multi-objective optimization approach that is primarily based on historical flight and taxi times but also includes certain airline, airport, and FAA priorities. The intent of this algorithm is to produce a more reliable, robust schedule that operates in today's environment as well as tomorrow's 4-Dimensional Trajectory Controlled system as described the FAA's Next Generation ATM system (NextGen). This novel airline schedule optimization approach is implemented using a multi-objective evolutionary algorithm which is capable of incorporating limited airport capacities. The core of the fitness function is an extensive database of historic operating times for flight and ground operations collected over a two year period based on ASDI and BTS data. Empirical distributions based on this data reflect the probability that flights encounter various flight and taxi times. The fitness function also adds the ability to define priorities for certain flights based on aircraft size, flight time, and airline usage. The algorithm is applied to airline schedules for two primary US airports: Chicago O'Hare and Atlanta Hartsfield-Jackson. The effects of this multi-objective schedule optimization are evaluated in a variety of scenarios including periods of high, medium, and low demand. The schedules generated by the optimization algorithm were evaluated using a simple queuing simulation model implemented in AnyLogic. The scenarios were simulated in AnyLogic using two basic setups: (1) using modes of flight and taxi times that reflect highly predictable 4-Dimensional Trajectory Control operations and (2) using full distributions of flight and taxi times reflecting current day operations. The simulation analysis showed significant improvements in reliability as measured by the mean square difference (MSD) of filed versus simulated flight arrival and departure times. Arrivals showed the most consistent improvements of up to 80% in on-time performance (OTP). Departures showed reduced overall improvements, particularly when the optimization was performed without the consideration of airport capacity. The 4-Dimensional Trajectory Control environment more than doubled the on-time performance of departures over the current day, more chaotic scenarios. This research shows that airline schedule reliability can be significantly improved over a network of airports using historical flight and taxi time data. It also provides for a mechanism to prioritize flights based on various airline, airport, and ATC goals. The algorithm is shown to work in today's environment as well as tomorrow's NextGen 4-Dimensional Trajectory Control setup.
Show less - Date Issued
- 2008
- Identifier
- CFE0002067, ucf:47572
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002067
