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Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.

BackgroundPulmonary vein isolation with wide antral ablation leads to better clinical outcomes for the treatment of atrial fibrillation, but the isolation lesion is invisible in conventional cryoballoon ablation. In this study, we aim to investigate the efficacy of the wide pulmonary vein isolation technique that includes the intervenous carina region, guided by high-density mapping, compared with pulmonary vein isolation alone without the mapping system.MethodsWe conducted a propensity score–matched comparison of 74 patients who underwent a wide cryoballoon ablation guided by high-density mapping (mapping group) and 74 controls who underwent conventional cryoballoon ablation in the same period (no-mapping group). The primary outcome was a clinical recurrence of documented atrial arrhythmias for >30 s during the 1-year follow-up.ResultsOf 74 patients in the mapping group, residual local potential in the pulmonary vein antrum was found in 30 (40.5%) patients, and additional cryothermal applications were performed to achieve a wide pulmonary vein isolation. Compared with the no-mapping group, the use of the mapping system in the mapping group was associated with a longer fluoroscopic time (26.97 ± 8.07 min vs. 23.76 ± 8.36 min, P = 0.023) and greater fluoroscopic exposure [339 (IQR181–586) mGy vs. 224 (IQR133–409) mGy, P = 0.012]. However, no significant differences between the two groups were found in terms of procedural duration and left atrial dwell time (104.10 ± 18.76 min vs. 102.45 ± 21.01 min, P = 0.619; 83.52 ± 17.01 min vs. 79.59 ± 17.96 min, P = 0.177). The rate of 12-month freedom from clinical atrial arrhythmia recurrence was 85.1% in the mapping group and 70.3% in the no-mapping group (log-rank P = 0.029).ConclusionVoltage and pulmonary vein potential mapping after cryoballoon pulmonary vein isolation can identify residual potential in the pulmonary vein antrum, and additional cryoablation guided by mapping leads to improved freedom from atrial arrhythmias compared with conventional pulmonary vein isolation without the mapping system.Clinical Trial Registration NumberChiCTR2200064383.

Background. Catheter ablation failure poses a clinical challenge for epicardial or intramural ventricular arrhythmia (VA); however, guidewire ablation within the coronary venous system (CVS) may be effective and safe for targeting VAs. Methods. The ex vivo phase included four steps. In step 1, the steam pop incidence rates during guidewire ablation at power settings of 5, 10, 15, 20, and 25 W were analyzed using 10 mm- and 20 mm-tip guidewires. In step 2, guidewire ablation was performed for application durations of 10, 20, 30, 40, 50, 60, and 90 s, and the lesion size was measured. In step 3, the effects of saline infusion (0, 1, 2, 3, and 4 mL/min) on lesion dimensions and steam pop formation were examined. In step 4, an orthogonal array was constructed to obtain the optimal guidewire ablation parameters. In the in vivo phase, guidewire ablation within the CVS was performed in three dogs, and the lesion features in 10 days after ablation were observed. Results. In step 1, the steam pop incidence rates at 5, 10, 15, 20, and 25 W were 0%, 0%, 12.5%, 62.5%, and 100% using the 10 mm-tip guidewires and 0%, 0%, 0%, 25%, and 75% using the 20 mm-tip guidewires, respectively. In step 2, we found that the lesion areas increased with an increase in the ablation duration (the maximum lesion diameters at 30, 60, and 90 s were 4.9 ± 0.4, 7.0 ± 0.8, and 9.2 ± 0.7 mm in the 10 mm group and 3.2 ± 0.5, 4.5 ± 0.4, and 5.3 ± 0.7 mm in the 20 mm-tip group, respectively). In step 3, we observed that saline infusion was negatively correlated with ablation lesions but had a lower risk of steam pop. The optimal parameters for the 20 mm-tip guidewire ablation were 15 W, 50 s, and 2 mL/min or 20 W, 70 s, and 2 mL/min. In the in vivo phase, effective ablation lesions with maximum and minimum diameters of 3.2 ± 0.3 and 2.8 ± 0.5 mm, respectively, were created by the guidewires during the 10-day observation period after ablation. Conclusion. This novel radiofrequency guidewire ablation technique can feasibly create effective lesions within the CVS, which may improve the efficacy of catheter ablation for challenging epicardial or intramural VA.

Single event transient (SET) induced by high energy single particle radiation is the main threat to space application electronic system reliability. The evaluation and measurement of SET is the key to improve the performance of radiation hardened intergrated circuit. In view of the single event transient generated by the combined circuit, an improved circuit-level simulation method combining charge collection sensitive volume (SV) and bipolar diffusion mechanism for SET with heavy ion incidence was presented. The physics based multi-node charge collection model was built by analyzing layout characteristics such as active region geometry and heavy ion incidence angle. As the charge sharing effect and parasitic bipolar amplification effect considered, the established method which was integrated in the developed TREES software was used for evaluating SET in the 65 nm commercial cell library. The results show that the SET cross sections and pulse width distribution can be calculated and compared, which offer reference data for SET filter design.