Velocity Relaxation Research Articles

Cardiovascular status in endogenous cortisol excess: the prospective CV-CORT-EX study.

Cushing´s syndrome (CS) results in increased cardiovascular morbidity and mortality. Subtype-specific differences and possible reversibility after biochemical cure are not well investigated. Prospective cohort study evaluating the cardiovascular status in different forms of endogenous cortisol excess. Patients with overt CS (n=40, 47±13 years, 75% women; 18 pituitary, 13 adrenal, 9 ectopic), biochemically cured CS (n=56, 53±12 years, 79% women; 30 pituitary, 21 adrenal, 5 ectopic), and adrenal incidentalomas with mild autonomous cortisol secretion (MACS) (n=18, 62±11 years, 56% women) underwent comprehensive biochemical, metabolic, and cardiovascular assessment. Results were compared with a representative sample of the general population of Würzburg (n=4965, 55±12 years, 52% women). Overt CS was associated with left ventricular (LV) remodeling along with hypertrophy and impaired longitudinal systolic/diastolic function at echocardiography. In 20 CS patients followed for a median of 8 (quartiles: 6, 11) months after biochemical remission, hypertension and hyperglycemia were better controlled, while cardiac alterations only partially improved. Patients with previous CS (median time of biochemical remission: 95 (36, 201) months) had worse diastolic function than the general population (LV relaxation velocity e´ 0.08 (0.07, 0.10) ms-1 vs 0.10 (0.08, 0.12) ms-1, p<0.001). In MACS, cardiac remodeling was even more pronounced than in individuals with metabolic syndrome. In patients with overt CS, cured CS, and MACS, we found a sizable and significant deviation from the general population mean regarding cardiac structure and function. Even mild cortisol excess is associated with glucocorticoid-induced cardiac alterations which appear to persist despite long-term biochemical remission.

Abstract 4113716: Natural shear wave imaging as a predictor for left ventricular pressures: Can they reflect raised filling pressures?

Background: Current conventional echocardiographic assessment of diastolic function relies on predicting left ventricular (LV) filling pressure as a surrogate of diastolic function. High frame rate (HFR) Shear wave (SW) imaging is emerging as an innovative parameter for assessing myocardial stiffness, a key determinant of diastolic function. Natural SW are induced by valve closure (i.e. mitral valve closure (MVC)). Little is known so far, to which extent SWs could reflect changes in diastolic LV filling pressures. Purpose: We aimed at investigating the relationship between natural SW after MVC and LV diastolic pressures in an attempt to set up a cut-off value beyond which, elevated LV pressure can be suspected indicating diastolic dysfunction. Methods: Thirty patients (mean age 68.4±9.9 years) scheduled for clinically indicated left heart catheterization were prospectively recruited. Left ventricular end-diastolic pressure (LVEDP) was measured during the catheterization. Immediately afterwards, conventional as well as HFR (1167 ±86 Hz) echocardiography was performed. We drew an anatomical M-mode along the anteroseptal wall in the parasternal long axis view from base to apex and the display was colour coded for tissue acceleration. SWs appeared immediately after MVC as tilted green bands and their propagation velocity was measured semi-automatically (Figure 1) . Results: LVEDP in our cohort ranged from 7.5 to 29.5 mmHg. From conventional echocardiographic parameters, only mitral inflow to mitral relaxation velocity ratio (E/e’) correlated moderately with LVEDP (r=0.51, p=0.006). SW velocities after MVC showed strong positive correlation with LVEDP (r=0.78, p&lt;0.001) (Figure 2) . A cut-off value for SW velocity of 5.8 m/s showed an excellent ability to discriminate normal from elevated LVEDP (AUC: 0.98; Sensitivity: 90%, specificity: 100%, accuracy: 97%) (Figure 3) . Conclusions: Our data showed that SW velocities at end-diastole after MVC could predict elevated LV filling pressures accurately. Natural shear wave imaging appears as a promising innovative tool for assessment of diastolic function.

Adipose tissue/ heart lipid transport determines cardiac diastolic function

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and often occurring in obese individuals. Previous research has demonstrated that the modification of lipid metabolism can prevent the onset of diastolic dysfunction. In our project we have investigated how lipid transport influences the onset of diastolic dysfunction utilizing heart- and adipose tissue-specific knockdowns of the fatty acid (FA) transport protein 1 (FatP1) in Drosophila melanogaster. Methods We generated Drosophila with heart-specific (+/+; Hand4.2-GAL4/UAS-FatP1; tdtK/+) (cFatP1-KD) and adipose tissue-specific (+/+; ppl-GAL4/UAS-FatP1; tdtK/+) (atFat-P1-KD) FatP1 knockdowns using the UAS/GAL4 system. The flies' cardiomyocytes endogenously express tdTomato, facilitating fluorescence-based live imaging of the heart by high-resolution video fluorescence microscopy, as previously described. Cardiac morphology and cardiac lipid accumulation was monitored by confocal microscopy. Additionally, mitochondrial function was evaluated using the glycolytic Seahorse assay of whole hearts. Results Blocking FA-uptake into adipose tissue in atFatP1-KD flies resulted in a highly significant reduction in relaxation velocity (p=0.0009, WT vs. atFatP1-KD), indicative of diastolic dysfunction in flies, while contraction velocity and fractional shortening (systolic function) remained unchanged. Diastolic dysfunction was associated with a significant increase of cardiac lipid droplet (LD) quantity and size in flies lacking FatP1 in adipose tissue (p=0.0275 and p&amp;lt;0.0001, respectively, WT vs. atFatP1-KD). Cardiac mitochondrial function was significantly impaired in atFatP1-KD flies compared to WT flies. Reducing cardiac FA uptake in heart-specific FatP1 KD flies led to a decrease in end-diastolic diameter and a significant reduction in relaxation and contraction velocity (p&amp;lt;0.0001 and p=0.0001, respectively, WT vs. cFatP1-KD), suggesting impairment in both diastolic and systolic function. Interestingly, the number of cardiac LDs increased in cFATP1-KD, however their size decreased significantly resulting in an overall unchanged lipid content compared to WT flies (p=0.0475 and p=0.0367, respectively, WT vs. atFatP1-KD). Mitochondrial function showed no significant alterations. Conclusion This study demonstrates that reducing FA-uptake in adipose or cardiac tissue results in cardiac dysfunction in Drosophila melanogaster. Reduction of adipose tissue FA-uptake results exclusively in diastolic dysfunction likely mediated by cardiac lipid overload and subsequent mitochondrial dysfunction. In contrast, blockade of Fatp1-mediated cardiac FA-uptake induces diastolic/ systolic dysfunction which was unrelated to alterations in cardiac lipid content and mitochondrial dysfunction suggesting alternative mechanisms. These study identifies FatP1-mediated FA-uptake in adipose tissue as a potential therapeutic target for the treatment of diastolic dysfunction.

The STRIPAK associated kinase MST4 is a novel mediator in heart failure pathogenesis

Abstract Heart failure still poses substantial challenges in understanding its underlying molecular pathways. We recently found the mammalian STE20-like kinase 4 (MST4) significantly upregulated in human failing hearts (5.7-fold in DCM and 3.8-fold ICM) as well as in heart failure animal models (i.e. 2.5-fold in Calsarcin-1-KO, 2.5-fold in MLP-KO). MST4 is a member of striatin interacting phosphatases and kinases complexes (STRIPAK), an emerging group of multiprotein complexes responsible for integrating cellular signalling pathways. We provide the first evidence of functional STRIPAK complexes containing MST4 by co-immunoprecipitation and interactomics experiments in cardiomyocytes. Moreover, we found MST4 to interact with several intercalated disc proteins like beta-Catenin or Desmin. Adenoviral overexpression of MST4 in neonatal rat ventricular cardiomyocytes (NRVCM) results in a significant increase in cell size (+13%). This was not accompanied by the activation of fetal genes such as NPPA, NPPB or RCAN1.4, but rather by an increase in phosphorylation of Protein kinase B (PKB/Akt, 3.3-fold). Akt is usually associated with physiological hypertrophy, indicating that MST4 may be involved in protective pathways in cardiomyocytes. In support of this notion, MST4 overexpression reduced apoptotic activity (cleavage of Caspase 3 -69%, Caspase 7 -80%, Parp1 -27%) and improved both contractility (fractional shortening cell +23%, fractional shortening sarcomere +30%, time to max. contraction cell -10%, time to max. contraction sarcomere -12%) and relaxation parameters (time to max. relaxation velocity cell -12%) in isolated adult rat ventricular cardiomyocytes. In order to identify cardiac targets of MST4, we performed a comprehensive analysis of the phosphoproteome of NRVCM overexpressing MST4 compared with control-virus +/- pharmacological inhibitor at two time points. We identified more than 70,000 peptides including more than 20,000 phosphopeptides in more than 4,000 protein groups. Using linear modelling with a reduced data set containing regulated features selected by thresholds for p-value and fold change, we observed a consistent MST4 effect and a number of enriched gene ontology terms. Here, we found several potential MST4 targets and effects on protein expression levels associated with intercalated disc proteins. In human heart samples, MST4 was also localized to the intercalated disc region by immunostaining. Interesting proteins in that context that might help explain some of the observed cardioprotective MST4 effects are Connexin 43, Desmin, Ryanodine receptor, Phospholemman, Junctophilin2, Myozap or Frizzled 1. Taken together, our data imply that MST4 upregulation in human heart failure serves an adaptive role which may offer translational opportunities.Graphical Abstract

Robust 3D multi‐material hydrodynamics using discontinuous Galerkin methods

AbstractA high‐order discontinuous Galerkin (DG) method is presented for nonequilibrium multi‐material () flow with sharp interfaces. Material interfaces are reconstructed using the algebraic THINC approach, resulting in a sharp interface resolution. The system assumes stiff velocity relaxation and pressure nonequilibrium. The presented DG method uses Dubiner's orthogonal basis functions on tetrahedral elements. This results in a unique combination of sharp multimaterial interfaces and high‐order accurate solutions in smooth single‐material regions. A novel shock indicator based on the interface conservation condition is introduced to mark regions with discontinuities. Slope limiting techniques are applied only in these regions so that nonphysical oscillations are eliminated while maintaining high‐order accuracy in smooth regions. A local projection is applied on the limited solution to ensure discrete closure law preservation. The effectiveness of this novel limiting strategy is demonstrated for complex three‐dimensional multi‐material problems, where robustness of the method is critical. The presented numerical problems demonstrate that more accurate and efficient multi‐material solutions can be obtained by the DG method, as compared to second‐order finite volume methods.

Hydrogel microsphere stem cell encapsulation enhances cardiomyocyte differentiation and functionality in scalable suspension system

A reliable suspension-based platform for scaling engineered cardiac tissue (ECT) production from human induced pluripotent stem cells (hiPSCs) is crucial for regenerative therapies. Here, we compared the production and functionality of ECTs formed using our scaffold-based, engineered tissue microsphere differentiation approach with those formed using the prevalent scaffold-free aggregate platform. We utilized a microfluidic system for the rapid (1 million cells/min), high density (30, 40, 60 million cells/ml) encapsulation of hiPSCs within PEG-fibrinogen hydrogel microspheres. HiPSC-laden microspheres and aggregates underwent suspension-based cardiac differentiation in chemically defined media. In comparison to aggregates, microspheres maintained consistent size and shape initially, over time, and within and between batches. Initial size and shape coefficients of variation for microspheres were eight and three times lower, respectively, compared to aggregates. On day 10, microsphere cardiomyocyte (CM) content was 27 % higher and the number of CMs per initial hiPSC was 250 % higher than in aggregates. Contraction and relaxation velocities of microspheres were four and nine times higher than those of aggregates, respectively. Microsphere contractile functionality also improved with culture time, whereas aggregate functionality remained unchanged. Additionally, microspheres displayed improved β-adrenergic signaling responsiveness and uniform calcium transient propagation. Transcriptomic analysis revealed that while both microspheres and aggregates demonstrated similar gene regulation patterns associated with cardiomyocyte differentiation, heart development, cardiac muscle contraction, and sarcomere organization, the microspheres exhibited more pronounced transcriptional changes over time. Taken together, these results highlight the capability of the microsphere platform for scaling up biomanufacturing of ECTs in a suspension-based culture platform.

Numerical simulation of jet break-up in the second-wind induced regime using the local front reconstruction method

In the second wind-induced regime, the jet deformations are influenced by aerodynamic instabilities acting on the jet surface. In addition, velocity relaxation in the liquid is an important mechanism with a strong influence on the violent break-up of laminar jets (i.e., the bursting). The exact interplay between the aerodynamic forces and the velocity profile relaxation is insufficiently described in the literature. Thus, we investigate numerically cylindrical liquid jets with fully developed and uniform velocity inlet profiles for different liquid and gas properties to elucidate the physical mechanisms governing the bursting of the jet. For this study, the gas-liquid interface is tracked using a front tracking technique: the Local Front Reconstruction Method (LFRM). In contrast with traditional front tracking techniques, LFRM allows for complex topological changes (merging and break-up) while keeping a sharp representation of the interface. The comparison of the obtained results with literature suggests that LFRM is a suitable technique for capturing the complex morphological deformations of a bursting jet. Additionally, we analyzed the influence of air and liquid properties on the jet deformations, which evidenced that velocity profile relaxation plays an important role in the complex process of break-up of the jet, that in combination with the destabilizing effect of the aerodynamic forces lead to the bursting of the jet.

Experimental Investigation of Slow Relaxation of Sound Velocity in Carbonate Rock

Experimental Investigation of Slow Relaxation of Sound Velocity in Carbonate Rock

Tissue Doppler ultrasound of arm muscles to assess myotonia in myotonic dystrophies: An exploratory study.

Myotonia is a key symptom of myotonic dystrophies (DM), and its quantification is challenging. This exploratory study evaluated the utility of tissue Doppler ultrasound (TDU) to assess myotonia in DM. Twelve DM patients (seven type-1 DM [DM1] and five type-2 DM [DM2]) and 20 age-matched healthy subjects were included in this cross-sectional study. After measuring cross-sectional areas of the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles in a resting state, muscle contraction/relaxation time, time to peak tissue velocity, peak tissue velocity and velocity gradients of these muscles were measured via TDU while performing forced fist unclenching after fist closure. Additionally, grip strength, Medical Research Council Sum score and patient-reported myotonia severity scores were assessed. DM1 and DM2 patients had a lower grip strength than healthy subjects (p = .0001/p = .002). Patient-reported myotonia did not differ between DM1 and DM2 patients. DM1 patients revealed FDS and EDC atrophy compared to DM2 patients and healthy subjects (p = .003/p = .004). TDU revealed prolonged muscle contraction and relaxation times in both DM subtypes, with prolonged time to reach FDS peak relaxation velocity and altered peak FDS relaxation velocity only in DM1 patients (p = .03/p = .003). Peak FDS relaxation velocity correlated inversely with C(C)TG repeat numbers in DM patients. Sensitivity of TDU parameters to detect myotonic dystrophy varied between 50% and 75%, with a specificity of 95%. Our exploratory study suggests that TDU could serve as a novel tool to quantify myotonia in DM patients, but larger follow-up studies are warranted to validate its diagnostic accuracy.

Abstract We013: Modeling Sex and Stress using Induced Pluripotent Stem Cell Derived Cardiomyocytes

Despite causing 1 in 3 deaths worldwide, cardiovascular disease and the heart have only recently been studied in women. Contrary to previous belief, the female heart is not just a smaller replica of a male heart. Almost all heart diseases show sexual differences in risk, treatment, and symptoms. Even with these differences there is a lack of female models in animal and cellular studies. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful human model to test baseline and stressed sex differences at the cellular level. We hypothesized that using stressors that mimic disease conditions (drugs, substrate stiffness) in multiple male and female hiPSC-CMs will result in differential sex-based responses. We ran Traction Force Microscopy on 3 male (n = 424 cells, 3 batches) and 3 female (n = 318 cells, 3 batches) cell lines on 10 kPa polyacrylamide hydrogels. Male cells had 42% higher twitch force (p = 8.8E-6) with 25% higher contraction (p = 1.77E-5) and relaxation (p = 0.0006) velocities. However, female cells had a larger spread area (823 +/- 17.32 µm 2 vs. 756 +/- 21.64 µm 2 , p = 0.0018). To validate hiPSC-CMs as a model we compared preliminary RNA-seq to publicly available Heart Cell Atlas sc/snRNA-seq data sets of primary ventricular cardiomyocytes. They had similar differentially expressed genes (DEGs) as our hiPSC-CMs. Furthermore, DEGs had significantly enriched gene sets including a 25-fold enrichment in hypertrophic cardiomyopathy (FDR = 1.6E-7), 23-fold in dilated cardiomyopathy (FDR = 1.6E-7), and 16-fold in cardiac muscle contraction (FDR = 6.3E-4). We analyzed stiffness by differentiating and culturing hiPSC-CMs on 10 kPa and 100 kPa stiffness hydrogels. Our RNA-seq analysis at day 10 and 30 after differentiation found 7000 DEGs at 10 kPa while only 556 DEGs at 100 kPa. We looked hypercontractility caused stres and performed RNA-seq on day 60 wild type and hypercontractile mutant hiPSC-CMs. The wild type was dosed with positive inotrope levosimendan to induce hypercontractility while the hypercontractile mutant was dosed with negative inotrope verapamil to lower contractility. Hypercontractility had significant upregulation of the cellular response to stress including ER stress, stress-activated MAPK cascades, stress fibers, and cardiac muscle hypertrophy in response to stress. These differences can identify possible gene targets for preventing cardiovascular disease and inform personalized medicine.

Abstract Tu039: Intestinal atrophy contributes to low-grade inflammation, cardiac dysfunction and metabolic syndrome-like phenotype in a model of heart failure with preserved ejection fraction.

Introduction: Heart failure with preserved ejection fraction (HFpEF) comprises half of all HF cases and lacks effective treatment. HFpEF is now seen as a systemic syndrome often linked to comorbidities like hypertension, obesity, and diabetes. These conditions are commonly associated with unhealthy diets rich in fats but lacking in fiber. We explored the effects of a 3-week exposure to excess mineralocorticoids, salt, and high fat diet (HFD) deficient in fiber. We hypothesize that these challenges lead to intestinal atrophy, contributing to low-grade inflammation that promotes the progression of heart failure and metabolic disease. Methods: We used a mix of 1% saline in drinking water and subcutaneous implantation of controlled-release DOCA pellets (0.83 mg/day) alongside a high-fat diet (60% fat) in 8-week-old female and male C57BL6/J mice. Control mice received a standard chow diet and regular water. Results: The challenge resulted in significant reductions in colon mass, colon length, crypt length, and mucus layer thickness compared to the control group. Additionally, elevated levels of C-reactive protein and IL-6 were detected in the plasma. These changes were accompanied by alterations in diastolic function, including decreased peak myocardial relaxation velocity (e'), elevated E/e' ratio, increased E/A ratio, and prolonged isovolumetric relaxation time (IVRT), while the ejection fraction (EF) remained unchanged. Contractility parameters, such as peak myocardial contraction velocity (s'), declined in challenged mice, along with diminished stroke volume (SV). We also found increased organ weight in the liver, spleen, and lungs indicative of organ congestion. Furthermore, signs of metabolic syndrome were identified, including increased body weight, increased adiposity characterized by gonadal and subcutaneous fat accumulation, and dysglycemia (see Data Table). Conclusions: Our data suggests that in this model, heart failure triggers intestinal hypoperfusion, resulting in intestinal atrophy and compromising the integrity of the intestinal lining. Additionally, a diet rich in fat and lacking in fiber alters the gut environment by diminishing mucus production and promoting a closer interaction between the microbiome and host cells. This compromised mucus layer and intestinal barrier facilitates bacterial wall products to move into the circulation, resulting in a pro-inflammatory state that subsequently affects both cardiac function and metabolism.

A second-order particle Fokker-Planck model for rarefied gas flows

The direct simulation Monte Carlo (DSMC) method has become a powerful tool for studying rarefied gas flows. However, for the DSMC method to be effective, the cell size must be smaller than the mean free path, and the time step smaller than the mean collision time. These constraints make it difficult to use the DSMC method in multiscale rarefied gas flows. Over the past decade, the particle Fokker-Planck (FP) method has been studied to address computational cost issues in the near-continuum regime. To capture the main features of the Boltzmann equation, various FP models have been proposed, such as the quadratic entropic FP (Quad-EFP) and the ellipsoidal statistical FP (ESFP). Nevertheless, few studies have clearly demonstrated that the FP method offers a computational advantage over the DSMC method without sacrificing accuracy. This is because conventional particle FP methods have employed first-order accuracy schemes. The present study proposes a unified stochastic particle ESFP (USP-ESFP) model. This model improves the accuracy of shear stress and heat flux predictions. Additionally, a spatial interpolation scheme is introduced to the particle FP method. The numerical test cases include relaxation problem, Couette flows, Poiseuille flows, velocity perturbation, and hypersonic flows around a cylinder. The results show that the USP-ESFP model agrees well with both analytical and DSMC results. Furthermore, the USP-ESFP model is found to be less sensitive to cell size and time step than the DSMC method, resulting in a factor of four speed-up for the considered hypersonic flow around a cylinder.

Contractility assessment using aligned human iPSC-derived cardiomyocytes

IntroductionCardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. MethodsAligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. ResultsWhen cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DiscussionTaken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.

Functional traits of the heart in post-infarction myocardial remodeling

The in vitro assessment of the functional peculiarities of heart failure (HF) linked to post-infarction remodeling of the myocardium in order to identify compensatory and decompensatory pathogenetic mechanisms. Material and methods. Myocardial infarction was reproduced in white laboratory rats by twice administration of isoproterenol (IMI). The functional state of the left ventricle (LV) of isolated heart was estimated at the end of the IMI model (initial) and after 4 weeks (the period of myocardial remodeling installing) in regard to following targets: study of myocardial inotropism to ET-1 action, including its effect on volume and resistance efforts, of myocardial tolerance to ischemia and reperfusion, as well as of coronary reactivity to various stimulations (eg, acetylcholine, bradykinin, adenosine, epoxyeicosatrienes). Results. Post-infarction remodeling of the myocardium was imposed by the reversal of ET-1 induced negative inotropic effect of the isolated heart to a positive response, manifested by increase in LV systolic pressure and cardiac output up to 10%. This improvement was associated with an increase of -dP/dTmax and +dP/dTmax values, indices of the isovolumic relaxation and contraction of the heart, by up to 9.3%, which led to a better hetero- and homeometric regulation of the heart, in particularly notable being the optimization of cardiac adaptation to resistance effort, including the condition of ET-1 premedication. The endothelium dependent coronary phenomenon Gregg was markedly improved such as the coronary functional reserve increased by up to 43% under the action of acetylcholine, adenosine and bradykinin. Remarkably, the post-infarction remodeling of the myocardium ensured a diminution of the B1-receptor mediated bradykinin induced coronary dilatation while the B2-receptors mediated bradykinin effect increased. Likewise, the increase of myocardium tolerance to ischemia (30 min) and reperfusion (45 min) was another disentangled benefit inherent to post-infarction remodeling, which was exhibited by significant lowered value of LV end-diastolic pressure. Conclusions. 1. The functional link of HF to post-infarction remodeling of the myocardium is outlined by the improvement of myocardial inotropism which led to appearance of the positive response to ET-1 manifested by the increase of LV systolic pressure and cardiac output. 2. Inotropic improvement was associated with an increase of isovolumic relaxation and contraction velocity, which contributed to the increased capacity of the homeometric regulation of the LV and of the heart adaptation to resistance effort as well. 3. An important pathophysiological hallmark of post-infarction HF is the increase of bradykinin induced coronary dilation mediated by B1 receptors, but its reduction in association with the increase of the coronary dilation mediated by B2 receptors is a prediction of a positive post-infarction remodeling of the myocardium and of HF evolution as well.

Energy-conserving finite difference scheme based on velocity interpolation applicable to unsteady flows using collocated grids

The collocation method uses the Rhie–Chow scheme to find the cell interface velocity by pressure-weighted interpolation. The accuracy of this interpolation method in unsteady flows has not been fully clarified. This study constructs a finite difference scheme for incompressible fluids using a collocated grid in a general curvilinear coordinate system. The velocity at the cell interface is determined by weighted interpolation based on the pressure difference to prevent pressure oscillations. The Poisson equation for the pressure correction value is solved with the cross-derivative term omitted to improve calculation efficiency. In addition, simultaneous relaxation of velocity and pressure is applied to improve convergence. Even without the cross-derivative term, calculations can be stably performed, and convergent solutions are obtained. In unsteady inviscid flow, the conservation of kinetic energy is excellent even in a non-orthogonal grid, and the calculation result has second-order accuracy to time. In viscous analysis at a high Reynolds number, the error decreases compared with that of the Rhie–Chow interpolation method. The present numerical scheme improves calculation accuracy in unsteady flows. The possibility of applying this computational method to high Reynolds number flows is demonstrated through several analyses.

Tissue Doppler imaging of the diaphragm and outcome of weaning from mechanical ventilation.

This study aimed to employ tissue Doppler imaging to monitor diaphragmatic peak velocity and acceleration during contraction and relaxation in mechanically ventilated patients, with the objective of assessing the potential utility of this technique in predicting weaning outcomes. A total of 89 adult subjects were recruited in this study. After 30 min of spontaneous breathing trial, the diaphragm motion parameters, including peak contraction velocity, peak relaxation velocity, contraction acceleration and relaxation acceleration, were measured in real time using tissue Doppler imaging. According to the results of weaning, the patients were divided into successful weaning group and failed weaning group. The differences of diaphragmatic tissue Doppler imaging monitoring indicators between the two groups were analysed, and the receiver operating characteristic curve was drawn to analyse the value of each ultrasound parameter in predicting weaning. In the successful weaning group, there were 61 subjects, while in the failed weaning group, there were 28 subjects. The peak contraction velocity, peak relaxation velocity, contraction acceleration and relaxation acceleration of the diaphragm were significantly higher in the failed weaning group compared to the successful weaning group (P < 0.05). The area under the curve of diaphragmatic peak contraction velocity, peak relaxation velocity, diaphragmatic contraction acceleration and diaphragmatic relaxation acceleration were 0.81 (0.72-0.91), 0.85 (0.77-0.93), 0.74 (0.63-0.86) and 0.86 (0.78-0.94), respectively. The diaphragm ultrasonic tissue Doppler imaging variables can serve as predictive indicators for weaning mechanical ventilation in patients, thus providing an effective tool to assist critical care physicians in determining the optimal timing for weaning mechanical ventilation.

Chelyshkov wavelet-based numerical technique for the solution of Darcy–Forchheimer flow of Erying–Powell radiated dusty fluid over a stretching sheet with Cattaneo–Christov heat flux

This article presents the Chelyshkov wavelet-based numerical technique (CWBNT) for the solution of the system of non-linear differential equations arising in the study of Darcy–Forchheimer flow of Erying–Powell radiated dusty fluid over a stretching sheet with Cattaneo–Christov heat flux. Initially, the proposed technique is implemented on the test problem having exact solution. The obtained results are highly accurate in comparison with the solutions obtained by shooting technique based Runge–Kutta Fehlberg 4th–5th order method. The proposed technique is applied to the governing equations of the considered dusty fluid problem. The results obtained for some fixed values of parameters resemble the previously published results. The comparisons validate the method. The flow behavior of dusty fluid is analyzed and the effect of various factors on the velocity and thermal attribute of the dust and fluid phase are studied. It is inferred that the Erying–Powell fluid parameters ε and α have entirely different effects on temperature, velocity profiles, and skin-friction coefficient. The local inertia parameter decreases the velocity and thermal relaxation parameter decreases the temperature. Enhancement in temperature ratio and radiation parameters escalates the temperature and Nusselt number. The proposed technique is simple, reliable, efficient tool to solve the differential equations arising in dusty fluid flow problems.

Temperature Dependent Behavior of Elastic and Ultrasonic Proprieties of Transition Metal Carbide Mo2C Superconductor

Abstract: Transition metal carbides exhibit peculiar chemical and physical properties, making them integral to industrial applications that demand performance under high temperatures In the case of the hexagonal transition metal carbide Mo2C superconductor, higher-order elastic constants were calculated to be temperature-dependent using an interactional potential model. Second-order elastic constants are used to determine other allied ultrasonic variables. Second-order coefficients are used to analyze the temperature variation of ultrasonic velocities along the z-direction of the superconductor. Furthermore, the temperature difference of Debye average velocity and thermal relaxation time are considered along the same direction. The temperature dependence of ultrasonic properties is explored in relation to thermal, elastic, and mechanical properties. Ultrasonic attenuation , resulting from phonon–phonon (p–p) interactions, is calculated at different temperatures .The study establishes that thermal conductivity is a core provider of the observed ultrasonic attenuation, particularly at higher temperatures. The mechanical and thermal properties of the Mo2C superconductor are superior at lower temperatures. Keywords:Transition metal carbide superconductor, Thermal conductivity, Ultrasonic properties, Elastic properties, Mechanical properties. PACS numbers: 43. 35. Cg; 62.20.Dc; 63.20.Kr.

Prediction of Rheological Parameters of Polymers by Machine Learning Methods

Introduction. All polymer materials and composites based on them are characterized by pronounced rheological properties, the prediction of which is one of the most critical tasks of polymer mechanics. Machine learning methods open up great opportunities in predicting the rheological parameters of polymers. Previously, studies were conducted on the construction of predictive models using artificial neural networks and the CatBoost algorithm. Along with these methods, due to the capability to process data with highly nonlinear dependences between features, machine learning methods such as the k-nearest neighbor method, and the support vector machine (SVM) method, are widely used in related areas. However, these methods have not been applied to the problem discussed in this article before. The objective of the research was to develop a predictive model for evaluating the rheological parameters of polymers using artificial intelligence methods by the example of polyvinyl chloride.Materials and Methods. This paper used k-nearest neighbor method and the support vector machine to determine the rheological parameters of polymers based on stress relaxation curves. The models were trained on synthetic data generated from theoretical relaxation curves constructed using the nonlinear Maxwell-Gurevich equation. The input parameters of the models were the amount of deformation at which the experiment was performed, the initial stress, the stress at the end of the relaxation process, the relaxation time, and the conditional end time of the process. The output parameters included velocity modulus and initial relaxation viscosity coefficient. The models were developed in the Jupyter Notebook environment in Python.Results. New predictive models were built to determine the rheological parameters of polymers based on artificial intelligence methods. The proposed models provided high quality prediction. The model quality metrics in the SVR algorithm were: MAE – 1.67 and 0.72; MSE – 5.75 and 1.21; RMSE – 1.67 and 1.1; MAPE – 8.92 and 7.3 for the parameters of the initial relaxation viscosity and velocity modulus, respectively, with the coefficient of determination R2 – 0.98. The developed models showed an average absolute percentage error in the range of 5.9 – 8.9%. In addition to synthetic data, the developed models were also tested on real experimental data for polyvinyl chloride in the temperature range from 20° to 60°C.Discussion and Conclusion. The approbation of the developed models on real experimental curves showed a high quality of their approximation, comparable to other methods. Thus, the k-nearest neighbor algorithm and SVM can be used to predict the rheological parameters of polymers as an alternative to artificial neural networks and the CatBoost algorithm, requiring less effort to preset adjustment. At the same time, in this research, the SVM method turned out to be the most preferred method of machine learning, since it is more effective in processing a large number of features

Genetic ablation of Lmp2 increases the susceptibility for impaired cardiac function.

Proteasome degradation is an integral part of cellular growth and function. Proteasomal intervention may mitigate adverse myocardial remodeling, but is associated with the onset of heart failure. Previously, we have demonstrated that increasing abundance of cardiac Lmp2 and its incorporation into proteasome complexes is an endogenous mechanism for proteasome regulation during hypertrophic remodeling of the heart induced by chronic ß-adrenoreceptor stimulation. Here, we investigated whether Lmp2 is required for myocardial remodeling not driven by inflammation and show that Lmp2 is a tipping element for growth and function in the heart but not for proteasome insufficiency. While it has no apparent impact under unchallenged conditions, myocardial remodeling without Lmp2 exacerbates hypertrophy and restricts cardiac function. Under chronic ß-adrenoreceptor stimulation, as seen in the development of cardiovascular disease and the manifestation of heart failure, genetic ablation of Lmp2 in mice caused augmented concentric hypertrophy of the left ventricle. While the heart rate was similarly elevated as in wildtype, myocardial contractility was not maintained without Lmp2, and apparently uncoupled of the ß-adrenergic response. Normalized to the exacerbated myocardial mass, contractility was reduced by 41% of the pretreatment level, but would appear preserved at absolute level. The lack of Lmp2 interfered with elevated 26S proteasome activities during early cardiac remodeling reported previously, but did not cause bulk proteasome insufficiency, suggesting the Lmp2 containing proteasome subpopulation is required for a selected group of proteins to be degraded. In the myocardial interstitium, augmented collagen deposition suggested matrix stiffening in the absence of Lmp2. Indeed, echocardiography of left ventricular peak relaxation velocity (circumferential strain rate) was reduced in this treatment group. Overall, targeting Lmp2 in a condition mimicking chronic ß-adrenoreceptor stimulation exhibited the onset of heart failure. Anticancer therapy inhibiting proteasome activity, including Lmp2, is associated with adverse cardiac events, in particular heart failure. Sparing Lmp2 may be an avenue to reduce adverse cardiac events when chronic sympathetic nervous system activation cannot be excluded.