An official website of the United States government
Abstract Ischemia is a major limiting factor in Vascularized Composite Allotransplantation (VCA) as irreversible muscular injury can occur after as early as 4-6 hours of static cold storage (SCS). Organ preservation technologies have led to the development of storage protocols extending rat liver ex vivo preservation up to 4 days. Development of such a protocol for VCAs has the added challenge of inherent ice nucleating factors of the graft, therefore this study focused on developing a robust protocol for VCA supercooling. Rodent partial hindlimbs underwent subnormothermic machine perfusion (SNMP) with several loading solutions, followed by cryoprotective agent (CPA) cocktail developed for VCAs. Storage occurred in suspended animation for 24h and VCAs were recovered using SNMP with modified Steen. This study shows a robust VCA supercooling preservation protocol in a rodent model. Further optimization is expected to allow for its application in a transplantation model, which would be a breakthrough in the field of VCA preservation.*Irina Filz von Reiterdank & Pierre Tawa Contributed equally.
more »
« less
Modeling energy depletion in rat livers using Nash equilibrium metabolic pathway analysis
Abstract The current gold standard of Static Cold Storage (SCS), which is static cold storage on ice (about + 4 °C) in a specialized media such as the University of Wisconsin solution (UW), limits storage to few hours for vascular and metabolically active tissues such as the liver and the heart. The liver is arguably the pinnacle of metabolism in human body and therefore metabolic pathway analysis immediately becomes very relevant. In this article, a Nash Equilibrium (NE) approach, which is a first principles approach, is used to model and simulate the static cold storage and warm ischemia of a proposed model of liver cells. Simulations of energy depletion in the liver in static cold storage measured by ATP content and energy charge are presented along with comparisons to experimental data. In addition, conversion of Nash Equilibrium iterations to time are described along with an uncertainty analysis for the parameters in the model. Results in this work show that the Nash Equilibrium approach provides a good match to experimental data for energy depletion and that the uncertainty in model parameters is very small with percent variances less than 0.1%.
more »
« less
- Award ID(s):
- 1941543
- PAR ID:
- 10471513
- Publisher / Repository:
- NSF
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 12
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract A significant number of investigations have been performed to develop and optimize cold plates for direct-to-chip cooling of processor packages. Many investigations have reported computational simulations using commercially available computational fluid dynamic tools that are compared to experimental data. Generally, the simulations and experimental data are in qualitative agreement but often not in quantitative agreement. Frequently, the experimental characterizations have high experimental uncertainty. In this study, extensive experimental evaluations are used to demonstrate the errors in experimental thermal measurements and the experimental artifacts during testing that lead to unacceptable inconsistency and uncertainty in the reported thermal resistance. By comparing experimental thermal data, such as the temperature at multiple positions on the processor lid, and using that data to extract a meaningful measure of thermal resistance, it is shown that the data uncertainty and inconsistency are primarily due to three factors: (1) inconsistency in the thermal boundary condition supplied by the thermal test vehicle (TTV) to the cold plate, (2) errors in the measurement and interpretation of the surface temperature of a solid surface, such as the heated lid surface, and (3) errors introduced by improper contact between cold plate and TTV. A standard thermal test vehicle (STTV) was engineered and used to provide reproducible thermal boundary conditions to the cold plate. An uncertainty analysis was performed in order to discriminate between the sources of inconsistencies in the reporting of thermal resistance, including parameters such as mechanical load distribution, methods for measuring the cold plate base, and TTV surface temperatures. A critical analysis of the classical thermal resistance definition was performed to emphasize its shortcomings for evaluating the performance of a cold plate. It is shown that the thermal resistance of cold plates based on heat exchanger theory better captures the physics of the heat transfer process when cold plates operate at high thermodynamic effectiveness.more » « less
-
Abstract System-level integration and optimization of food-energy-water systems (FEWS) require coordination of multiple agencies and decision-makers and incorporating their interdependence. In general, such coordination might be hard to achieve. As a result, the literature on FEWS management either optimizes the operations for one sector (or one decision-maker), or models interdependence among the sectors without optimizing their operations. In this article, we develop a novel multi-agent management optimization approach that is able to incorporate stochasticity and uncertainty in the system’s dynamics and interdependence of the water and energy resources for food production. The proposed method is the first attempt to utilize fundamentals of decision and game theories to optimize operations of multi-agent FEWS. We specifically focus on differentiating between (1) cooperative decision optimization of the operations, where all decision-makers cooperate to achieve the best outcome for the whole system, the social optimum, and (2) non-cooperative decision-making of the agents, the Nash equilibrium. Illustrating with a real-world case study of FEWS in Ventura County, California, we show the difference between the cooperative and non-cooperative decision making in terms of long-term expected cost of managing the system. We further show how the extra costs associated with utilizing the renewable sources of water and energy could be incentivised, so that the non-cooperative solution (the Nash equilibrium) would naturally converge to the best outcome for the whole system (the social optimum).more » « less
-
Automated marker makers (AMMs) are decentralized exchanges that enable the automated trading of digital assets. Liquidity providers (LPs) deposit digital tokens, which can be used by traders to execute trades, which generate fees for the investing LPs. In AMMs, trade prices are determined algorithmically, unlike classical limit order books. Concentrated liquidity market makers (CLMMs) are a major class of AMMs that offer liquidity providers flexibility to decide not onlyhow muchliquidity to provide, butin what ranges of pricesthey want the liquidity to be used. This flexibility can complicate strategic planning, since fee rewards are shared among LPs. We formulate and analyze a game theoretic model to study the incentives of LPs in CLMMs. Our main results show that while our original formulation admits multiple Nash equilibria and has complexity quadratic in the number of price ticks in the contract, it can be reduced to a game with a unique Nash equilibrium whose complexity is only linear. We further show that the Nash equilibrium of this simplified game follows a waterfilling strategy, in which low-budget LPs use up their full budget, but rich LPs do not. Finally, by fitting our game model to real-world CLMMs, we observe that in liquidity pools with risky assets, LPs adopt investment strategies far from the Nash equilibrium. Under price uncertainty, they generally invest in fewer and wider price ranges than our analysis suggests, with lower-frequency liquidity updates. In such risky pools, by updating their strategy to more closely match the Nash equilibrium of our game, LPs can improve their median daily returns by $116, which corresponds to an increase of 0.009% in median daily return on investment (ROI). At maximum, LPs can improve daily ROI by 0.855% when they reach Nash equilibrium. In contrast, in stable pools (e.g., of only stablecoins), LPs already adopt strategies that more closely resemble the Nash equilibrium of our game.more » « less
-
In this paper, we study the problem of distributed generalized stochastic Nash equilibrium seeking for robot systems over a connected undirected graph. We use the cost functions containing uncertainty to represent the system’s performance under varying conditions. To mitigate the challenges posed by this uncertainty, we employ the Tikhonov regularization scheme, which also helps us to relax the strongly monotone condition of the cost functions to the strictly monotone condition. We also consider the inequality constraints, which represent the feasible working space of robots. Additionally, auxiliary parameters are introduced in the control laws to facilitate seeing the variational generalized stochastic Nash equilibrium. The convergence of the proposed control laws is analyzed by using the operator splitting method. Finally, we demonstrate the effectiveness of the proposed algorithm through an example involving multiple robots connected through a communication network.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41598-022-06966-2
