A pairwise maximum entropy model describes energy landscape for spiral wave dynamics of cardiac fibrillation

Heart is an electrically-connected network. Spiral wave dynamics of cardiac fibrillation shows chaotic and disintegrated patterns while sinus rhythm shows synchronized excitation patterns. To determine functional interactions between cardiomyocytes during complex fibrillation states, we applied a pairwise maximum entropy model (MEM) to the sequential electrical activity maps acquired from the 2D computational simulation of human atrial fibrillation. Then, we constructed energy landscape and estimated hierarchical structure among the different local minima (attractors) to explain the dynamic properties of cardiac fibrillation. Four types of the wave dynamics were considered: sinus rhythm; single stable rotor; single rotor with wavebreak; and multiple wavelet. The MEM could describe all types of wave dynamics (both accuracy and reliability>0.9) except the multiple random wavelet. Both of the sinus rhythm and the single stable rotor showed relatively high pairwise interaction coefficients among the cardiomyocytes. Also, the local energy minima had relatively large basins and high energy barrier, showing stable attractor properties. However, in the single rotor with wavebreak, there were relatively low pairwise interaction coefficients and a similar number of the local minima separated by a relatively low energy barrier compared with the single stable rotor case. The energy landscape of the multiple wavelet consisted of a large number of the local minima separated by a relatively low energy barrier, showing unstable dynamics. These results indicate that the MEM provides information about local and global coherence among the cardiomyocytes beyond the simple structural connectivity. Energy landscape analysis can explain stability and transitional properties of complex dynamics of cardiac fibrillation, which might be determined by the presence of 'driver' such as sinus node or rotor.Comment: Presented at the 62nd Biophysical Society Annual Meeting, San Francisco, California, 201

Characteristic Analysis of Wind Turbine Gearbox Considering Non-Torque Loading

In the design of wind turbine gearboxes, the most important objective is to improve the durability to guarantee a service life of more than 20 years. This work investigates how external loads caused by wind fluctuation influence both the load distribution over the gear tooth flank and the planet load sharing. A whole system model is developed to analyze a wind turbine gearbox (WTG) that consists of planetary gearsets. Two models for different design loads are employed to quantify how external loads acting on the input shaft of the WTG affect the load distribution of the gears and the load sharing among the planets under quasi-static conditions. One model considers only the torque for the design load, whereas the other model also considers non-torque loads. For two models, the results for the gear mesh misalignment, contact pattern, load distribution, and load sharing are different, and this leads to different gear safety factors. Therefore, the results indicate that it is appropriate to consider the non-torque loads in addition to the torque as the design load for a WTG, and that this is very important to accurately determine the design load that guarantee the service life of a WTG

Enhanced ferroelectric switching speed of Si-doped HfO2 thin film tailored by oxygen deficiency

Investigations concerning oxygen deficiency will increase our understanding of those factors that govern the overall material properties. Various studies have examined the relationship between oxygen deficiency and the phase transformation from a nonpolar phase to a polar phase in HfO2 thin films. However, there are few reports on the effects of oxygen deficiencies on the switching dynamics of the ferroelectric phase itself. Herein, we report the oxygen- deficiency induced enhancement of ferroelectric switching properties of Si-doped HfO2 thin films. By controlling the annealing conditions, we controlled the oxygen deficiency concentration in the ferroelectric orthorhombic HfO2 phase. Rapid high-temperature (800 degrees C) annealing of the HfO2 film accelerated the characteristic switching speed compared to low-temperature (600 degrees C) annealing. Scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) revealed that thermal annealing increased oxygen deficiencies, and first-principles calculations demonstrated a reduction of the energy barrier of the polarization flip with increased oxygen deficiency. A Monte Carlo simulation for the variation in the energy barrier of the polarization flipping confirmed the increase of characteristic switching speed

Randomized Comparison of Four-Times-Daily versus Once-Daily Intravenous Busulfan in Conditioning Therapy for Hematopoietic Cell Transplantation

AbstractSixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean ± SD) was 2.75 ± 0.22 versus 2.83 ± 0.21 hours, estimated daily AUC was 6058.0 ± 1091.9 versus 6475.5 ± 1099.4 μM·min per day, and clearance was 2.05 ± 0.36 versus 1.91 ± 0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU

Hematopoietic Differentiation of Embryoid Bodies Derived from the Human Embryonic Stem Cell Line SNUhES3 in Co-culture with Human Bone Marrow Stromal Cells

Human embryonic stem (ES) cells can be induced to differentiate into hematopoietic precursor cells via two methods: the formation of embryoid bodies (EBs) and co-culture with mouse bone marrow (BM) stromal cells. In this study, the above two methods have been combined by co-culture of human ES-cell-derived EBs with human BM stromal cells. The efficacy of this method was compared with that using EB formation alone. The undifferentiated human ES cell line SNUhES3 was allowed to form EBs for two days, then EBs were induced to differentiate in the presence of a different serum concentration (EB and EB/high FBS group), or co-cultured with human BM stromal cells (EB/BM co-culture group). Flow cytometry and hematopoietic colony-forming assays were used to assess hematopoietic differentiation in the three groups. While no significant increase of CD34+/CD45- or CD34+/CD38- cells was noted in the three groups on days 3 and 5, the percentage of CD34+/CD45- cells and CD34+/CD38- cells was significantly higher in the EB/BM co-culture group than in the EB and EB/high FBS groups on day 10. The number of colony-forming cells (CFCs) was increased in the EB/BM co-culture group on days 7 and 10, implying a possible role for human BM stromal cells in supporting hematopoietic differentiation from human ES cell-derived EBs. These results demonstrate that co-culture of human ES-cell-derived EBs with human BM stromal cells might lead to more efficient hematopoietic differentiation from human ES cells cultured alone. Further study is warranted to evaluate the underlying mechanism