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Breakdown of the blood-central nervous system barrier (BCNSB) is a hallmark of many neuroinflammatory disorders, such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), we show that endothelial-to-mesenchymal transition (EndoMT) occurs in the CNS before the onset of clinical symptoms and plays a major role in the breakdown of BCNSB function. EndoMT can be induced by an IL-1β-stimulated signaling pathway in which activation of the small GTPase ADP ribosylation factor 6 (ARF6) leads to crosstalk with the activin receptor-like kinase (ALK)-SMAD1/5 pathway. Inhibiting the activation of ARF6 both prevents and reverses EndoMT, stabilizes BCNSB function, reduces demyelination, and attenuates symptoms even after the establishment of severe EAE, without immunocompromising the host. Pan-inhibition of ALKs also reduces disease severity in the EAE model. Therefore, multiple components of the IL-1β-ARF6-ALK-SMAD1/5 pathway could be targeted for the treatment of a variety of neuroinflammatory disorders.

This study presents a model-based dynamic optimization strategy for a dual-mode CO2 heat pump coupled with hot and cold thermal storages, which was proposed as a high-efficiency smart grid enabling option in heating and cooling services for buildings or industry. Dynamic optimal control for simultaneously charging of hot and cold thermal storages is very delicate. The optimal control of compressor discharge pressure were commonly used for optimal control of heat pump systems. In this study, the outlet water temperatures of hot and cold tanks are used as indicators in the dynamic optimal strategy for charging of hot and cold storages using a dual-mode heat pump. The Modelica based dynamic model of the coupled system was developed and validated. To optimize the overall coefficient of performance (COP) during energy process, the transient total COP is optimized by genetic algorithm based on Modelica-based modeling of dynamic system. A dynamic optimal control strategy was developed and implemented into an experimental system. Test results show that this developed model-based dynamic optimal control strategy is able to search the optimal transient total COP and optimize the overall COP of such coupled systems during energy charging; and the optimal results is better than those obtained using another two experiment-based methods.

A dual-mode CO2 heat pump coupled with hot and cold thermal storages was proposed as a high-efficiency smart grid enabling option for supporting higher penetration levels of intermittent renewables in the energy system. However, the optimal control of simultaneous hot and cold thermal storage systems in real time is very delicate. In this study, a novel system-based optimization method is proposed, in which the COP of such system is simplified with empirical correlation, and a solution for the optimal control vector that maximize the transient system COP is determined using genetic algorithm for global optimization. To evaluate the system-based optimization method, experimental tests were conducted, and a real-time near-optimal control strategy for charging of dual-model energy storage systems was developed and implemented. Practical operation results show that the near-optimal control strategy is able to search the near-optimal transient total COP in real time, and optimize the overall COP of such dual-mode coupled systems during energy charging.

This paper presents an experimental study of the performances of a dual-mode CO 2 heat pump system with thermal storage. This CO 2 system was tested at a variable frequency compressor, variable expansion valve opening as well as variable frequency cooling/heating water pumps. It is found that the performances of CO 2 heat pump with thermal storage can be optimized through optimizing thermal stratification of thermal storage tank coupled with heat pump system performances. High compressor frequency benefits the system performances. Expansion valve opening affects the thermal stratification of thermal storage tanks very slightly. The overall COP reaches a maximum when heating and cooling water flow rates were set as 0.1 m 3 /h and 0.2 m 3 /h respectively at compressor frequency of 50 Hz and expansion valve opening of 330 pulses.