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Key points: In adult ventricular myocytes, the slow delayed rectifier (IKs) channels are distributed on the surface sarcolemma, not t‐tubules.In adult ventricular myocytes, KCNQ1 and KCNE1 have distinct cell surface and cytoplasmic pools.KCNQ1 and KCNE1 traffic from the endoplasmic reticulum to the plasma membrane by separate routes, and assemble into IKs channels on the cell surface.Liquid chromatography/tandem mass spectrometry applied to affinity‐purified KCNQ1 and KCNE1 interacting proteins reveals novel interactors involved in protein trafficking and assembly.Microtubule plus‐end binding protein 1 (EB1) binds KCNQ1 preferentially in its dimer form, and promotes KCNQ1 to reach the cell surface.An LQT1‐associated mutation, Y111C, reduces KCNQ1 binding to EB1 dimer. Slow delayed rectifier (IKs) channels consist of KCNQ1 and KCNE1. IKs functions as a 'repolarization reserve' in the heart by providing extra current for ventricular action potential shortening during β‐adrenergic stimulation. There has been much debate about how KCNQ1 and KCNE1 traffic in cells, where they associate to form IKs channels, and the distribution pattern of IKs channels relative to β‐adrenergic signalling complex. We used experimental strategies not previously applied to KCNQ1, KCNE1 or IKs, to provide new insights into these issues. 'Retention‐using‐selected‐hook' experiments showed that newly translated KCNE1 constitutively trafficked through the conventional secretory path to the cell surface. KCNQ1 largely stayed in the endoplasmic reticulum, although dynamic KCNQ1 vesicles were observed in the submembrane region. Disulphide‐bonded KCNQ1/KCNE1 constructs reported preferential association after they had reached cell surface. An in situ proximity ligation assay detected IKs channels in surface sarcolemma but not t‐tubules of ventricular myocytes, similar to the reported location of adenylate cyclase 9/yotiao. Fluorescent protein‐tagged KCNQ1 and KCNE1, in conjunction with antibodies targeting their extracellular epitopes, detected distinct cell surface and cytoplasmic pools of both proteins in myocytes. We conclude that, in cardiomyocytes, KCNQ1 and KCNE1 traffic by different routes to surface sarcolemma where they assemble into IKs channels. This mode of delayed channel assembly helps IKs fulfil its function of repolarization reserve. Proteomic experiments revealed a novel KCNQ1 interactor, microtubule plus‐end binding protein 1 (EB1). EB1 dimer (active form) bound KCNQ1 and increased its surface level. An LQT1 mutation, Y111C, reduced KCNQ1 binding to EB1 dimer. Key points: In adult ventricular myocytes, the slow delayed rectifier (IKs) channels are distributed on the surface sarcolemma, not t‐tubules.In adult ventricular myocytes, KCNQ1 and KCNE1 have distinct cell surface and cytoplasmic pools.KCNQ1 and KCNE1 traffic from the endoplasmic reticulum to the plasma membrane by separate routes, and assemble into IKs channels on the cell surface.Liquid chromatography/tandem mass spectrometry applied to affinity‐purified KCNQ1 and KCNE1 interacting proteins reveals novel interactors involved in protein trafficking and assembly.Microtubule plus‐end binding protein 1 (EB1) binds KCNQ1 preferentially in its dimer form, and promotes KCNQ1 to reach the cell surface.An LQT1‐associated mutation, Y111C, reduces KCNQ1 binding to EB1 dimer. [ABSTRACT FROM AUTHOR]

Heat exchanger designers need reliable thermal-hydraulic correlations to optimize heat exchanger designs. This work combines an adaptive sampling method with a Computational Fluid Dynamics (CFD) simulator to obtain increased accuracy and validity range of heat transfer and pressure drop predictions using a limited number of data points. Correlation efficacy was evaluated based on a steam generator case study. The sensitivity to the design parameters was analyzed in detail. The RMSE (root mean square error) of the developed correlations were reduced, through CFD sampling, from 28% to 15% for pressure drop, and from 33% to 25% heat transfer, compared to regression on experimental data only. The best reference correlations have RMSE values of 43% and 33% on pressure drop and heat transfer, respectively, on an independent validation set. Indeed, a radically different fin-tube geometry was suggested for the case study, compared to results using the Escoa correlations.The developed correlations show good to excellent agreement with trends in the CFD model. The quantitative error of predicted heat transfer and pressure drop coefficients at the case study optimum, however, was as large as those of the Escoa correlations. More data are likely needed to improve accuracy for compact heat exchanger designs further. [ABSTRACT FROM AUTHOR]

Blood volume analysis provides a quantitative volume assessment in patients with equivocal or discordant clinical findings. Reports on its use in mechanical circulatory support are limited and it has never been described in patients with a total artificial heart. Our series demonstrates that patients supported with total artificial heart as a bridge to transplant have significant reductions in red blood cell volume and heterogeneous adaptations in their total blood volume and plasma volume. Pathologic derangements in our patient's total blood volume were targeted to restore euvolemia., Competing Interests: Disclosure: M.A.S. is a Medical Advisor for Daxor Corporation (Oak Ridge, TN). F.A.A. is a consultant for SynCardia Systems (Tucson, AZ). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)