Optimization of 3D controlled ELM-free state with recovered global confinement for KSTAR with n=1 resonant magnetic field perturbation

Mitigation of deleterious heat flux from edge-localized modes (ELMs) on fusion reactors is often attempted with 3D perturbations of the confining magnetic fields. However, the established technique of resonant magnetic perturbations (RMPs) also degrades plasma performance, complicating implementation on future fusion reactors. In this paper, we introduce an adaptive real-time control scheme on the KSTAR tokamak as a viable approach to achieve an ELM-free state and simultaneously recover high-confinement (βN~1.91, βp~1.53, and H98~0.9), demonstrating successful handling of a volatile complex system through adaptive measures. We show that, by exploiting a salient hysteresis process to adaptively minimize the RMP strength, stable ELM suppression can be achieved while actively encouraging confinement recovery. This is made possible by a self-organized transport response in the plasma edge which reinforces the confinement improvement through a widening of the ion temperature pedestal and promotes control stability, in contrast to the deteriorating effect on performance observed in standard RMP experiments. These results establish the real-time approach as an up-and-coming solution towards an optimized ELM-free state, which is an important step for the operation of ITER and reactor-grade tokamak plasmas.

Protein Palmitoylation in Bovine Ovarian Follicle

Protein palmitoylation is a reversible post-translational modification by fatty acids (FA), mainly a palmitate (C16:0). Palmitoylation allows protein shuttling between the plasma membrane and cytosol to regulate protein stability, sorting and signaling activity and its deficiency leads to diseases. We aimed to characterize the palmitoyl-proteome of ovarian follicular cells and molecular machinery regulating protein palmitoylation within the follicle. For the first time, 84 palmitoylated proteins were identified from bovine granulosa cells (GC), cumulus cells (CC) and oocytes by acyl-biotin exchange proteomics. Of these, 32 were transmembrane proteins and 27 proteins were detected in bovine follicular fluid extracellular vesicles (ffEVs). Expression of palmitoylation and depalmitoylation enzymes as palmitoyltransferases (ZDHHCs), acylthioesterases (LYPLA1 and LYPLA2) and palmitoylthioesterases (PPT1 and PPT2) were analysed using transcriptome and proteome data in oocytes, CC and GC. By immunofluorescence, ZDHHC16, PPT1, PPT2 and LYPLA2 proteins were localized in GC, CC and oocyte. In oocyte and CC, abundance of palmitoylation-related enzymes significantly varied during oocyte maturation. These variations and the involvement of identified palmitoyl-proteins in oxidation-reduction processes, energy metabolism, protein localization, vesicle-mediated transport, response to stress, G-protein mediated and other signaling pathways suggests that protein palmitoylation may play important roles in oocyte maturation and ffEV-mediated communications within the follicle.

Pediatric interfacility transport effects on mortality and length of stay

Background We aimed to evaluate the effects of interfacility pediatric critical care transport response time, physician presence during transport, and mode of transport on mortality and length of stay (LOS) among pediatric patients. We hypothesized that a shorter response time and helicopter transports, but not physician presence, are associated with lower mortality and a shorter LOS. Methods Retrospective, single-center, cohort study of 841 patients (< 19 years) transported to a quaternary pediatric intensive care unit and cardiovascular intensive care unit between 2014 and 2018 utilizing patient charts and transport records. Multivariate linear and logistic regression analyses adjusted for age, diagnosis, mode of transport, response time, stabilization time, return duration, mortality risk (pediatric index of mortality-2 and pediatric risk of mortality-3), and inotrope, vasopressor, or mechanical ventilation presence on admission. Results Four hundred and twenty-eight (50.9%) patients were transported by helicopter, and 413 (49.1%) were transported by ambulance. Physicians accompanied 239 (28.4%) transports. The median response time was 2.0 (interquartile range 1.4–2.9) hours. Although physician presence increased the median response time by 0.26 hours (P = 0.020), neither physician presence nor response time significantly affected mortality, ICU length of stay (ILOS) or hospital length of stay (HLOS). Helicopter transports were not significantly associated with mortality or ILOS, but were associated with a longer HLOS (3.24 days, 95% confidence interval 0.59–5.90) than ambulance transports (P = 0.017). Conclusions These results suggest response time and physician presence do not significantly affect mortality or LOS. This may reflect the quality of pre-transport care and medical control communication. Helicopter transports were only associated with a longer HLOS. Our analysis provides a framework for examining transport workforce needs and associated costs.

Structural Basis for Allosteric Control of the SERCA-Phospholamban Membrane Complex by Ca2+ and Phosphorylation

Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca2+-transport response to β-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca2+ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN’s cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme’s active site, augmenting Ca2+ transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally-modified bitopic membrane proteins.

Structural Basis for Allosteric Control of the SERCA-Phospholamban Membrane Complex by Ca2+ and cAMP-dependent Phosphorylation

Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca2+-transport response to β-adrenergic stimulation, thus modulating cardiac output during the fight- or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), keeping this enzyme’s function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca2+ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN’s cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme’s active site, augmenting Ca2+ transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally-modified bitopic membrane proteins.

Recent nitrate transport response to extreme weather conditions in the Bode lower-mountain range catchment, central Germany

&lt;p&gt;There is mounting evidence that the extreme weather conditions, either droughts or floods, could likely be more frequent than what was thought before, resulting in increased impacts on our ecosystems. This study aims to investigate the effect of the extreme drought events that occurred in the period 2015-2019 on the nitrate-N concentrations and loads in the Bode catchment (3300 km&lt;sup&gt;2&lt;/sup&gt;) located in the transition areas of central uplands and northern lowlands of Germany. To this, a combination of high-frequency (15 min data in the period 2011-2019) and long-term (1993-2010) of continuous discharge and biweekly nitrate-N records in five typical gauging stations, representing different landscape features and dominant-runoff components of the catchment, were utilized. In the period 2015-2019, mean annual precipitation decreased by about 10%, and mean temperature increased by 1.46 &amp;#176;C compared to the period 1969-2014. Results suggested no evident changes in nitrate-N concentrations and loads in the upper mountainous areas of the Bode catchment (mainly forest) and groundwater-dominated gauging station, reflecting no impact of the droughts on these two archetypical sub-catchments. However, results showed that the nitrate-N concentrations and loads declined significantly in the lowland, agriculture dominated areas of the Bode catchment. This can be explained by the reduction of nitrate-N contribution from the lower part of the catchment during the spring and summer periods. It seems that the drought-induced increased evapotranspiration and decreased precipitation resulted in the reduced runoff from lowland areas of the catchment, affecting the nitrate-N mixing of different N source areas within the catchment. These findings suggest that recent changes of temperature and precipitation unlikely change considerably nitrate-N dynamics in terms of yearly load, but significantly reduce nitrate-N concentrations during low-flow periods in summer.&amp;#160;&amp;#160;&lt;/p&gt;

A Strong Role for the AMOC in Partitioning Global Energy Transport and Shifting ITCZ Position in Response to Latitudinally Discrete Solar Forcing in CESM1.2

Ocean circulation responses to interhemispheric radiative imbalance can damp north–south migrations of the intertropical convergence zone (ITCZ) by reducing the burden on atmospheric energy transport. The role of the Atlantic meridional overturning circulation (AMOC) in such dynamics has not received much attention. Here, we present coupled climate modeling results that suggest AMOC responses are of first-order importance to muting ITCZ shift magnitudes as a pair of hemispherically asymmetric solar forcing bands is moved from equatorial to polar latitudes. The cross-equatorial energy transport response to the same amount of interhemispheric forcing becomes systematically more ocean-centric when higher latitudes are perturbed in association with strengthening AMOC responses. In contrast, the responses of the Pacific subtropical cell are not monotonic and cannot predict this variance in the ITCZ’s equilibrium position. Overall, these results highlight the importance of the meridional distribution of interhemispheric radiative imbalance and the rich buffering of internal feedbacks that occurs in dynamic versus thermodynamic (slab) ocean modeling experiments. Mostly, the results imply that the problem of developing a theory of ITCZ migration is entangled with that of understanding the AMOC’s response to hemispherically asymmetric radiative forcing—a difficult topic deserving of focused analysis across more climate models.