Amplitude Of Events Research Articles

Simulation of modern and future climate by INM-CM6M

Abstract The paper considers the results of climate change modelling for 1850–2100 using the INM-CM6M climate model of the Marchuk Institute of Numerical Mathematics of the Russian Academy of Sciences. The calculations were performed according to the CMIP6 protocol for modelling the present-day climate for the period from 1850 to 2014 and the IPCC scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5 of anthropogenic forcing changes in 2015–2100. We analyse changes in such characteristics of the climate system as global mean near-surface temperature, spatial distributions of near-surface temperature, precipitation, sea level pressure, and radiative forcing characteristics in comparison with observational data and results obtained with the previous (INM-CM5) version of the model. We conclude that the new version of the model is superior to the previous one in terms of the quality of simulation of the observed climate and its changes in 1960–2022. The amplitude of global warming predicted by the INM-CM6M for moderate IPCC scenarios is close to the average value of the CMIP6 model ensemble, and for severe scenarios it is closer to the upper limit of its range. For the SSP3-7.0 and SSP5-8.5 scenarios, INM-CM6M predicts a complete loss of Arctic sea ice in summer. As the rate of global warming increases, so does the amplitude and duration of extreme weather and climate events.

Projected Changes to Characteristics of El Niño‐Southern Oscillation, Indian Ocean Dipole, and Southern Annular Mode Events in the CMIP6 Models

AbstractIn this study we analyse projections of future changes to the El Niño Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), and Southern Annular Mode (SAM) using the latest generation of climate models. Multiple future scenarios are considered. We quantify the fraction of models that project future increases or decreases in the frequency and amplitude of ENSO, IOD, and SAM events in the late 21st century. Changes to the frequency of co‐occurring and consecutive driver phases are also examined. We find that while there is large inter‐model spread, the most common pathways correspond to more frequent ENSO events; weaker, less frequent IOD events; and stronger, but less frequent austral spring SAM events. There is no clear consensus on the change to the frequency of concurrent events, though we find a significant increase in La Niña‐ and El Niño‐only events occurring with neutral IOD and SAM. We also find a significant increase to the frequency of consecutive positive IOD events under a high emissions scenario, but no significant change to the frequency of consecutive ENSO or negative IOD events. In most models, the correlation between drivers, that is, ENSO and IOD, and ENSO and SAM, does not significantly change between the late 20th and late 21st century. These results indicate a high degree of internal variability in the models.

Exploring climate stabilisation at different global warming levels in ACCESS-ESM-1.5

Abstract. Under the Paris Agreement, signatory nations aim to keep global warming well below 2 °C above pre-industrial levels and preferably below 1.5 °C. This implicitly requires achieving net-zero or net-negative greenhouse gas emissions to ensure long-term global temperature stabilisation or reduction. Despite this requirement, there have been few analyses of stabilised climates, and there is a lack of model experiments to address our need for understanding the implications of the Paris Agreement. Here, we describe a new set of experiments using the Australian Community Climate and Earth System Simulator Earth system model (ACCESS-ESM-1.5) that enables the analysis of climate evolution under net-zero emissions, and we present initial results. Seven 1000-year-long simulations were run with global temperatures stabilising at levels in line with the Paris Agreement and at a range of higher global warming levels (GWLs). We provide an overview of the experimental design and use these simulations to demonstrate the consequences of delayed attainment of global net-zero carbon dioxide emissions. We show that there are substantial differences between transient and stabilising climate states and differences in stabilisation between GWLs. As the climate stabilises under net-zero emissions, we identify significant and robust changes in temperature and precipitation patterns including continued Southern Ocean warming and changes in regional precipitation trends. Changes under net-zero emissions differ greatly between regions, including contrasting trajectories of sea ice extent between the Arctic and Antarctic. We also examine the El Niño–Southern Oscillation (ENSO) and find evidence of reduced amplitude and frequency of ENSO events under climate stabilisation relative to projections under transient warming. An analysis at specific GWLs shows that significant regional changes continue for centuries after emission cessation and that these changes are stronger at higher GWLs. Our findings suggest substantial long-term climate changes are possible even under net-zero emission pathways. These simulations are available for use in the community and will hopefully motivate further experiments and analyses based on other Earth system models.

Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.

A Predictive Model for Treatment Effectiveness in Severe Primary Immune Thrombocytopenia during Pregnancy: A Retrospective Study in a Tertiary Critical Maternity Referral Center

Objectives: The study aimed to identify factors influencing the severity of primary immune thrombocytopenia (ITP) during pregnancy, develop a predictive model for treatment response, and report maternal and neonatal outcomes associated with severe ITP. Design: A retrospective analysis was conducted on 155 pregnancies with severe ITP between January 2018 and April 2023 at a tertiary critical maternity referral center in Shanghai, China. Participants/Materials: The study included 155 pregnancies diagnosed with severe ITP, divided into groups based on the lowest platelet count (<30 × 109/L vs. 30–50 × 109/L) and first-line treatment response (non-response vs. response). Setting: The study was conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine, a tertiary critical maternity rescue referral center. Methods: Clinical characteristics and outcomes were compared between groups. A multivariable logistic regression model was used to identify factors associated with the severity of ITP. A prediction model for treatment response was established using LASSO-logistic regression and internally validated. Results: ITP severity was found to be correlated with low maximum amplitude of thromboelastography (OR 5.43, 95% CI: 1.48–16.00, p = 0.002), bleeding events (OR 4.91, 95% CI: 1.62–14.86, p = 0.005), and low reticulocytes (OR 2.40 × 10−7, 95% CI: 1.06 × 10−13 to 0.55, p = 0.04). Of the 118 patients who received first-line therapy, 52 (44%) responded. The dataset was randomly split into a training (N = 99) and test (N = 23) set with a ratio of 8:2. A predictive nomogram was created and internally validated showing good discrimination. The model yielded an area under receiver operating characteristic curve of 0.78 (0.69–0.87) and 0.85 (0.67–1.00) in the training and validation cohort, respectively. Earlier delivery and high rate of neonatal intensive care unit admission occurred with severe ITP and treatment failure. Limitations: The study was limited by a relatively small sample size and the retrospective observational design, which imposed limitations on the assessment of treatment efficacy. Conclusions: We identified clinical predictors of ITP severity and treatment resistance during pregnancy. A nomogram predicting first-line response was validated. These findings can facilitate clinical decision-making and counseling regarding this challenging pregnancy complication.

Chile Niño/Niña in the coupled model intercomparison project phases 5 and 6

The north and central coast of Chile is influenced by El Niño-Southern Oscillation (ENSO) through oceanic and atmospheric teleconnections. However, it also experiences episodic oceanic warmings off central Chile (30°S) lasting a few months that are not necessarily associated with ENSO. These episodes, called “Chile Niño” events, besides their ecological and socio-economical impacts, have also the potential to influence tropical Pacific variability. Here, we investigate how realistically the models in the Coupled Model Intercomparison Project (CMIP, Phases 5 and 6) simulate Chile Niño/Niña (CN) events, and quantify their changes under anthropogenic forcing. Despite limitations of the global models in simulating realistically coastal upwelling dynamics, we show that they simulate reasonably well the observed spatial pattern, amplitude and seasonal evolution of CN events. They however fail to properly represent the positive skewness from observations. The analysis of a sub-group of models (36) that simulate ENSO realistically reveals that CN events increase in amplitude and variance in the future climate with no changes in their frequency of occurence. This is interpreted as resulting from compensating effects amongst changes in remote drivers and local feedbacks. In particular, ENSO variance increases while that of the South Pacific Oscillation decreases. Conversely, we found that while the Wind-Evaporation-SST feedback tends to increase and the coupling between mixed-layer depth and SST weakens, favoring the development of CN events, the thermocline and wind-SST feedbacks decrease. However, only the change in the thermocline feedback is correlated to changes in CN variance amongst the models, suggesting a dominant role of local oceanic stratification changes in constraining the sensitivity of CN to global warming.

Evaluation of Modeled Diurnal Warming Estimates for Application to Producing Sea Surface Temperature Analyses

AbstractAccurate knowledge of the amount of diurnal warming present in sea surface temperature (SST) observations at different times and effective depths is important for multiple applications including the production of blended SST analyses. This work explores the ability of a modified Kantha‐Clayson‐type one‐dimensional mixed layer ocean model with wave effects to accurately simulate the observed diurnal warming amplitude over a global grid when forced with coarse resolution numerical weather prediction (NWP) outputs. The sensitivity of the modeled diurnal amplitudes to multiple adjustable parameters and model configurations is evaluated to determine whether a preferred configuration can be identified that yields reliable predictions. The accuracy of the predictions is determined through comparison against estimates from operational SST retrievals from geostationary satellites. The results show that a single configuration can yield predictions that reproduce the observed range of diurnal warming amplitudes across a range of seasons and locations and an accurate occurrence frequency of the largest amplitude events. Simulated amplitudes fall along the one‐to‐one line with observations but with significant scatter due to factors including positioning of the NWP fluxes. The identified configuration is also shown to favorably reproduce diurnal warming observations from multiple research cruises. Overall uncertainty of the simulated diurnal warming amplitude across the different tests ranges between 0.4 K for all observations to ∼1 K for the largest warming events. While the focus is not on model comparisons, the results show improved performance relative to other models. Use of the model appears warranted but the associated uncertainty must be considered.

Non-spatial hippocampal behavioral timescale synaptic plasticity during working memory is gated by entorhinal inputs.

Behavioral timescale synaptic plasticity (BTSP) is a form of synaptic potentiation where the occurrence of a single large plateau potential in CA1 hippocampal neurons leads to the formation of reliable place fields during spatial learning tasks. We asked whether BTSP could also be a plasticity mechanism for generation of non-spatial responses in the hippocampus and what roles the medial and lateral entorhinal cortex (MEC and LEC) play in driving non-spatial BTSP. By performing simultaneous calcium imaging of dorsal CA1 neurons and chemogenetic inhibition of LEC or MEC while mice performed an olfactory working memory task, we discovered BTSP-like events which formed stable odor-specific fields. Critically, the success rate of calcium events generating a significant odor-field increased with event amplitude, and large events exhibited asymmetrical formation with the newly formed odor-fields preceding the timepoint of their induction event. We found that MEC and LEC play distinct roles in modulating BTSP: MEC inhibition reduced the frequency of large calcium events, while LEC inhibition reduced the success rate of odor-field generation. Using two-photon calcium imaging of LEC and MEC temporammonic axons projecting to CA1, we found that LEC projections to CA1 were strongly odor selective even early in task learning, while MEC projection odor-selectivity increased with task learning but remained weaker than LEC. Finally, we found that LEC and MEC inhibition both slowed representational drift of odor representations in CA1 across 48 hours. Altogether, odor-specific information from LEC and strong odor-timed activity from MEC are crucial for driving BTSP in CA1, which is a synaptic plasticity mechanism for generation of both spatial and non-spatial responses in the hippocampus that may play a role in explaining representational drift and one-shot learning of non-spatial information.

Effect of Ambient Lighting on Intraocular Pressure Rhythms in Rats.

The purpose of this study was to determine the effects of ambient lighting on intraocular pressure (IOP) rhythmicity and variability. IOP was continuously recorded by wireless telemetry from rats under light/dark (LD), dark/light (DL), asymmetric (6L18D and 18D6L), constant dark (DD), and constant light (LL) cycles. In some DD experiments, 1-hour light pulses were presented at varying times. IOP rhythmicity and variability were respectively quantified via cosinor analysis and peak detection algorithms that identified transient and sustained fluctuations. Rat IOP peaked at night and troughed during the day with LD amplitude of 8.7 ± 3.4mm Hg. Rhythmicity persisted in DD and LL with a free-running period of 24.1 ± 0.3 and 25.2 ± 0.4 hours, respectively. Peak-to-trough amplitude was approximately 60% smaller in LL, often disappeared after 1 to 2 weeks as daytime IOP drifted 2.6 ± 1.5mm Hg higher, and returned to approximately 60% larger in LD. Rhythmicity was similarly impacted but resynchronized to DL over 4 to 6days. Rhythmicity was unaltered by short photoperiods (6L18D), but the nocturnal IOP elevation was markedly shortened by long photoperiods (18L6D) and temporarily lowered to daytime levels by light pulses during the subjective night. Transient and sustained event rate, amplitude, interval, and energy content were nearly identical in LD, DD, and LL. Aqueous humor dynamics of rat eyes are intrinsically configured to set IOP at daytime levels. Circadian clock input modulates these dynamics to elevate IOP at night. Light at night blocks this input, sending IOP back to daytime levels. Effects of abnormal lighting on IOP rhythmicity may contribute to pressure-related ocular neuropathies.

Unlocking Single Particle Anisotropy in Real‐Time for Photoelectrochemistry Processes at the Nanoscale

AbstractThe key to rationally and rapidly designing high‐performance materials is the monitoring and comprehension of dynamic processes within individual particles in real‐time, particularly to gain insight into the anisotropy of nanoparticles. The intrinsic property of nanoparticles typically varies from one crystal facet to the next under realistic working conditions. Here, we introduce the operando collision electrochemistry to resolve the single silver nanoprisms (Ag NPs) anisotropy in photoelectrochemistry. We directly identify the effect of anisotropy on the plasmonic‐assisted electrochemistry at the single NP/electrolyte interface. The statistical collision frequency shows that heterogeneous diffusion coefficients among crystal facets facilitate Ag NPs to undergo direction‐dependent mass transfer toward the gold ultramicroelectrode. Subsequently, the current amplitudes of transient events indicate that the anisotropy enables variations in dynamic interfacial electron transfer behaviors during photothermal processes. The results presented here demonstrate that the measurement precision of collision electrochemistry can be extended to the sub‐nanoparticle level, highlighting the potential for high‐throughput material screening with comprehensive kinetics information at the nanoscale.

Unlocking Single Particle Anisotropy in Real-Time for Photoelectrochemistry Processes at the Nanoscale.

The key to rationally and rapidly designing high-performance materials is the monitoring and comprehension of dynamic processes within individual particles in real-time, particularly to gain insight into the anisotropy of nanoparticles. The intrinsic property of nanoparticles typically varies from one crystal facet to the next under realistic working conditions. Here, we introduce the operando collision electrochemistry to resolve the single silver nanoprisms (Ag NPs) anisotropy in photoelectrochemistry. We directly identify the effect of anisotropy on the plasmonic-assisted electrochemistry at the single NP/electrolyte interface. The statistical collision frequency shows that heterogeneous diffusion coefficients among crystal facets facilitate Ag NPs to undergo direction-dependent mass transfer toward the gold ultramicroelectrode. Subsequently, the current amplitudes of transient events indicate that the anisotropy enables variations in dynamic interfacial electron transfer behaviors during photothermal processes. The results presented here demonstrate that the measurement precision of collision electrochemistry can be extended to the sub-nanoparticle level, highlighting the potential for high-throughput material screening with comprehensive kinetics information at the nanoscale.

Extreme events and extreme multistability in a nearly conservative system.

This study investigates the emergence of extreme events in a complex variable dynamical system. In the absence of an external forcing, the model exhibits nearly Hamiltonian dynamics. When we set the system to a nearly conservative state and perturb it with external forcing, the formation of the onset of the extreme events was detected. By applying nullcline analysis and the system's vector field, we explored the underlying mechanism that leads to extreme events. Furthermore, we have conducted a thorough investigation to show the dynamic origins of extreme amplitude events and their transitions. The hardware electronic experiment is used to validate the numerical results of the onset of extreme events, and the results obtained are in good agreement with one another.

The Frequency Characteristics of Vibration Events in an Underground Coal Mine and Their Implications on Rock Burst Monitoring and Prevention

The main frequency of microseismic signals has recently been identified as a dominant indicator for characterizing vibration events because it reflects the energy level of these events. Frequency information directly determines whether effective signals can be collected, which has a significant impact on the accuracy of predicting rock burst disasters. In this study, we adopted a characterizing method and developed a monitoring system for capturing rock failure events at various strata in an underground coal mine. Based on the rock break mechanism and energy release level, three types of rock failure events, namely, high roof breaking, low roof breaking, and coal fracture events, were evaluated separately using specific sensors and monitoring systems to optimize the monitoring accuracy and reduce the general cost. The captured vibration signals were processed and statistically analyzed to characterize the main frequency features for different rock failure events. It was found that the main frequency distribution ranges of low roof breaking, high roof breaking, and coal fracture events are 20–400 Hz, 1–180 Hz, and 1–800 Hz, respectively. Therefore, these frequency ranges are proposed to monitor different vibration events to improve detection accuracy and reduce the test and analysis times. The failure mechanism in a high roof is quite different from that of low roof failure and coal fracturing, with the main frequency and amplitude clustering in a limited zone close to the origin. Coal fracturing and lower roof failure show a synergistic effect both in the maximum amplitude and main frequency, which could be an indicator to distinguish failure locations in the vertical direction. This result can support the selection and optimization of the measurement range and main frequency parameters of microseismic monitoring systems. This study also discussed the distribution law of the maximum amplitude and main frequency of different events and the variation in test values with the measurement distance, which are of great significance in expanding the application of optimized microseismic monitoring systems for rock burst monitoring and prevention.

KLHL17 differentially controls the expression of AMPA- and KA-type glutamate receptors to regulate dendritic spine enlargement.

Kelch-like family member 17 (KLHL17), an actin-associated adaptor protein, is linked to neurological disorders, including infantile spasms and autism spectrum disorders. The key morphological feature of Klhl17-deficient neurons is impaired dendritic spine enlargement, resulting in the amplitude of calcium events being increased. Our previous studies have indicated an involvement of F-actin and the spine apparatus in KLHL17-mediated dendritic spine enlargement. Here, we show that KLHL17 further employs different mechanisms to control the expression of two types of glutamate receptors, that is, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and kainate receptors (KARs), to regulate dendritic spine enlargement and calcium influx. We deployed proteomics to reveal that KLHL17 interacts with N-ethylmaleimide-sensitive fusion protein (NSF) in neurons, with this interaction of KLHL17 and NSF enhancing NSF protein levels. Consistent with the function of NSF in regulating the surface expression of AMPAR, Klhl17 deficiency limits the surface expression of AMPAR, but not its total protein levels. The NSF pathway also contributes to synaptic F-actin distribution and the dendritic spine enlargement mediated by KLHL17. KLHL17 is known to act as an adaptor mediating degradation of the KAR subunit GluK2 by the CUL3 ubiquitin ligase complex, and Klhl17 deficiency impairs activity-dependent degradation of GluK2. Herein, we further demonstrate that GluK2 is critical to the increased amplitude of calcium influx in Klhl17-deficient neurons. Moreover, GluK2 is also involved in KLHL17-regulated dendritic spine enlargement. Thus, our study reveals that KLHL17 controls AMPAR and KAR expression via at least two mechanisms, consequently regulating dendritic spine enlargement. The regulatory effects of KLHL17 on these two glutamate receptors likely contribute to neuronal features in patients suffering from certain neurological disorders.

Variability of the Indian Ocean Dipole post-2100 reverses to a reduction despite persistent global warming

Previous examination of the Indian Ocean Dipole (IOD) response to greenhouse warming shows increased variability in the eastern pole but decreased variability in the western pole before 2100. The opposing response is due to a shallowing equatorial thermocline promoting sea surface temperature (SST) variability in the east, but a more stable atmosphere decreasing variability in equatorial zonal winds that weakens SST variability in the west. Post-2100, how the IOD may change remains unknown. Here we show that IOD variability weakens post-2100 in majority of models under a long-term high emission scenario to 2300. Post-2100, the atmosphere stability increases further and persistent ocean warming arrests or even reverses the eastern Indian Ocean shallowing thermocline. These changes conspire to drive decreased variability in both poles, reducing amplitude of moderate, strong and early-maturing positive IOD events. Our result highlights a nonlinear response of the IOD to long-term greenhouse warming under the high emission scenario.

The effect of mechanical ventilation compared to high-flow nasal cannula on gastric residual volume and reflux events using novel automated technology

Background & aimHigh flow nasal cannula (HFNC) oxygen therapy is frequently used following extubation. A case report, utilizing an innovative medical technology (The smART+ Platform, ART MEDICAL Ltd., Netanya, Israel) that enables the detection of gastric refluxes and gastric residual volumes (GRV), has suggested that HFNC may be associated with increased reflux events and GRV. This study measured reflux events and GRV using smART+ in mechanically ventilated patients before and after extubation while they were receiving HFNC therapy. We aim to show if there a significant difference in reflux events and GRV between HFNC users and mechanically ventilated patients. MethodsThis is a post hoc analysis examines data of a randomized controlled trial (RCT) involving critically ill adult patients who received enteral nutrition through the smART+ Platform. The study was approved by the local ethics committee. We compared the frequency and amplitude of reflux events and GRV in mechanically ventilated patients. These parameters were assessed both three hours before extubation and subsequently after extubation when the patients were connected to HFNC. Patients served as their own controls. To evaluate the differences between the pre- and post-extubation measurements, we applied a parametric paired t-test. ResultsTen patients (mean age of 58 years; mean APACHE II score 22; mean 3.9 days mechanical ventilation) were included. Three hours prior extubation the mean GRV was 4.1 ml/h compared to 14.03 ml/h on HFNC (p=0.004). The mean frequency of major reflux events was 2.33/h in ventilated patients versus 4.4/h in the HFNC patients (p=0.73). The mean frequency of major reflux events was 9.17/h in ventilated patients versus 9.83/h in HFNC patients (p=0.14). ConclusionsLeveraging the smART+ Platform, we demonstrated that the use of HFNC significantly increases GRV compared with patients on mechanical ventilation and may increase the frequency of major reflux events, thereby increasing risk of aspiration. Further studies are required to support our conclusions.

Comparative study on fracture evolution in steel fibre and bar reinforced concrete beams using acoustic emission and digital image correlation techniques

In recent decades, the demand for sustainable construction practices has increased, but raw materials such as reinforcing steel remain scarce. Therefore, steel fibres have emerged as a popular and sustainable choice in the construction industry, offering a cost-effective alternative to traditional steel bar reinforcement for both flatwork and elevated structures. The purpose of this study is therefore to compare the performance of fracture behaviour between steel fibre-reinforced concrete (SFRC) and steel bar-reinforced concrete (SBRC) beams subjected to three-point bending. The fracture process was monitored by using two non-invasive techniques: acoustic emission (AE) and digital image correlation (DIC). The damage level was identified by characterizing the parameter-based AE data such as hit rate, energy release, count, rise time, amplitude, and signal strength. DIC images were employed to visualise the crack propagation in parallel with the AE data. To further understand the fracture characteristics, the integration of 2D source localization of AE events (based on local AE fracture energies) with DIC results was investigated. The parameter-based AE results showed that SBRC beam experienced a high density of AE hits with large peak amplitude events that were accelerated during the pre-peak loading phase. The Ib-value analysis revealed that SBRC beam exhibited a higher degree of fracture magnitude during the primary crack development process than SFRC beam. Following the main cracking stage, SFRC beam demonstrated an improved post-cracking softening behavior and superior ability to arrest crack propagation compared to SBRC beam. The integration of local AE fracture energy and DIC results provided a novel approach for a better understanding of the fracture behaviour in both SFRC and SBRC beams. This study’s findings contribute to more precise monitoring of fracture evolution in SFRC and SBRC beams, ultimately improving the selection process for primary reinforcement in flatwork and elevated structures.

Contribution Of TRPV4 Channels To Calcium Signaling Profiles Of The Lung Microvascular Endothelium Under Acidic pH

Maintenance of lung endothelial barrier integrity is achieved to a great extent through effcient homeostatic endothelial calcium signaling in the lung microvasculature. The transient receptor potential vanilloid 4 (TRPV4), a non-selective calcium permeable channel has been implicated in several pulmonary pathologies involving lung barrier disruption. These channels are activated by various physical forces and chemical stimuli, but their underlying contribution to inherent and distinct microvascular endothelial Ca2+ signaling profiles are unknown. We previously assessed the role of TRPV4 channels in basal Ca2+ signaling dynamics of the pulmonary microcirculation under differing conditions of stretch and temperature. In the current study, we evaluate the impact of acidic pH (7.1, resembling acidosis) on the distinct endothelial Ca2+ signaling events in the mouse lung microcirculation and examine the participation of TRPV4 channels. Lung slices isolated from the Cdh5-GCaMP8 mice (transgenic mice with Ca2+-dependent fluorescent indicator expressed specifically within vascular endothelial cells) were mounted on Sylgard inserts with HEPES buffer (pH 7.45) and imaged for their basal signaling events using spinning disk confocal microscopy. After an initial baseline recording, the bathing solution was replaced with acidic HEPES buffer (pH 7.1) and recordings were made for approximately two minutes at 5 frames per second. These slices were then treated with the TRPV4 channel inhibitor GSK2193874 (3μM) or vehicle. The recorded image sequences were analyzed by using ImageJ and our custom signal tracking software S8, for quantification of the Ca2+ signaling profiles through event frequency, amplitude, duration and spread. Subjecting the lung slices to pH 7.1 increased the amplitude and spatial spread of the signaling events but the duration and frequency of the events remained relatively constant when compared to baseline recorded events. Addition of the channel blocker diminished the signaling event frequency, amplitude and spatial spread of the lung tissues. The normal pH and vehicle control for the above experiments did not show any relative change from the baseline signaling event profiles. To summarize, treating the lung slices to acidic pH increased the event amplitude and event spatial area distributions, indicating widespread activation of Ca2+ entry events. These increased event parameters were reduced upon addition of the antagonist, suggesting higher contribution of TRPV4 channel induced Ca2+ signaling events under acidic pH. We conclude that the channels contribute minimally to basal dynamics under homeostatic conditions but are activated to a greater extent under stimulations resembling pathological conditions like acidosis or acid aspirations. NIH P01 HL066299, R01 HL155288, NIH S10 0D020149. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic Hypoxia during Gestation Disrupts Spontaneous Ca2+ Oscillations in Middle Cerebral Arterial Myocytes of Fetal Sheep

Long Term Hypoxic (LTH) stress is associated with an elevated risk of intracranial hemorrhage and stroke in newborns. Existing evidence illustrates that fetal sheep subjected to LTH conditions exhibit compromised cerebrovascular reactivity and arterial development, leading to perturbations in cerebral blood flow. Given the critical role of whole-cell Ca2+ waveforms in the contraction of middle cerebral arterial (MCA) myocytes and the regulation of cerebral blood flow, a comprehensive understanding of Ca2+ signaling patterns can provide insight into hypoxia-related cerebrovascular disease in neonates. This study was designed to test the hypothesis that intrauterine LTH disrupts whole-cell Ca2+ oscillations in fetal MCA myocytes. The hypothesis was addressed using MCAs isolated from term fetal sheep (approximately 140 days of gestation) delivered by cesarean section. These fetuses were carried by ewes residing at low-altitude (700 m) or high-altitude conditions (3801 m) for over 100 days of gestation. Ca2+ oscillatory activity was recorded using confocal fluorescence imaging techniques in an en face myocyte preparation. Spontaneous Ca2+ oscillations were evaluated in the presence and absence of 30 mM K+ to depolarize the myocytes, with or without 10 μM ryanodine, which blocks ryanodine receptor mediated Ca2+ release. The results of the study reveal that LTH decreases oscillatory activity and restricts the augmentation of activity following membrane depolarization. Furthermore, LTH induces dysregulation in spatial and temporal Ca2+ signals, manifesting as reduced event amplitude, shortened event duration, and decreased area under the curve (AUC). These findings highlight the impact of gestational hypoxia on multiple aspects of Ca2+ signaling in fetal lamb MCA, which may contribute to cerebrovascular dysfunction in the newborn. R01HL155295, R01HL149608, Advanced Imaging and Microscopy Core Loma Linda University School of Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The response to ENSO under global warming

This investigation explores the impact of global warming on the El Nio-Southern Oscillation (ENSO), a pivotal climatic phenomenon with far-reaching consequences for worldwide weather patterns and ecosystems. In the context of ongoing endeavors to mitigate climate change, comprehending ENSO's response assumes a position of utmost significance. Current research suggests that the amplitudes of ENSO events may intensify in response to elevated temperatures, linked to non-linear increments in atmospheric water vapor. Furthermore, careful analysis reveals an augmented variability in sea surface temperature (SST) fluctuations during the 21st century compared to prior periods. The research also sheds light on the concurrent existence and interactions of Eastern Pacific (EP) and Central Pacific (CP) ENSO variations in the context of a warming climate. Ongoing investigations are committed to unraveling the intricacies of these phenomena and their implications for future climatic patterns. Nevertheless, uncertainties persist regarding the drivers of CP-type ENSO and heightened amplitudes, with some attributing these changes to global warming while others associate them with multidecadal rhythms.