Endothelial permeability has been extensively investigated in the context of pathologies such as cancer and also in studies of drug delivery from the circulation. Hypoxia is a critical regulator of endothelial cell (EC) behavior and affects the barrier function of endothelial linings, yet its role has been little studied. This paper reveals the effect of hypoxia on the permeability of an EC monolayer by cellular experiments using a microfluidic device and a conventional cell culture dish. Human umbilical vein endothelial cells (HUVECs) were seeded into one microfluidic channel, creating an EC monolayer on each vertical surface of a collagen gel confined to a central chamber. Oxygen tension was regulated to produce normoxic (21% O) or hypoxic (3% O) conditions by the supply of gas mixtures of oxygen, carbon dioxide, and nitrogen at predefined ratios into channels fabricated into the device. Permeability of the EC monolayer quantified by analyzing diffusion of fluorescence-labelled dextrans into the collagen gel increases with barrier function loss by 6 hour hypoxic exposure, showing 11-fold and 4-fold increases for 70 kDa and 10 kDa dextrans, respectively, on average. Consistent with this, subsequent immunofluorescent staining and separate western blot analysis of HUVECs on a culture dish demonstrate loose cell-cell adhesion resulting from internalization of VE-cadherin under hypoxia. Thus, hypoxic stress increases endothelial permeability by altering cell-cell junction integrity.

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According to the current Boiling Water Reactor (BWR) accident management procedure, the Reactor Pressure Vessel (RPV) is not depressurized until the core water level has decreased to a predetermined threshold level (e.g., 10% of the active fuel length from the bottom of the active fuel (BAF)) when the backup low pressure water injection is unavailable. In the meantime, significant Fission Products (FPs) may be released due to core degradation. In such case, excessive FP deposition on the RPV dome may lead to heat up and failure of the top flange sealing of the Primary Containment Vessel (PCV) due to radiation heat. For BWR4/Mark-I TQUV event, the relationship between the different depressurization timings and FP release and depositions (represented by CsI and CsOH) on RPV (especially, steam dryer and RPV dome), D/W, W/W have been highlighted with MELCOR-2.2 analyses. Overall, it may be understood that the later the depressurization timing, the later the RPV failure timing, but the larger the amount of FP released to RPV. The remaining FP not trapped by water pool were mostly deposited on the RPV steam dryer. Clear correlation between the FP deposition amount on the steam dryer and its temperature could be confirmed. However, more investigations may be necessary to reveal what determines the RPV dome temperature, which seemed to have limited influence on the D/W head temperature profile.

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