Human Neutrophil Elastase Degrades SPLUNC1 and Impairs Airway Epithelial Defense against Bacteria

Background:Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare. One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection. However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood. As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).Methodology/Main Results:Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE. To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells. The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi. We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.Conclusions:Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. © 2013 Jiang et al

Circinus X-1: survivor of a highly asymmetric supernova

We have analyzed the kinematical parameters of Cir X-1 to constrain the nature of its companion star, the eccentricity of the binary and the pre-supernova parameter space. We argue that the companion is most likely to be a low-mass (< 2.0 M_sun) unevolved star and that the eccentricity of the orbit is 0.94 +/- 0.04. We have evaluated the dynamical effects of the supernova explosion and we find it must have been asymmetric. On average, we find that a kick of 740 km/s is needed to account for the recently measured radial velocity of +430 km/s (Johnston, Fender & Wu) for this extreme system. The corresponding minimum kick velocity is 500 km/s. This is the largest kick needed to explain the motion of any observed binary system. If Cir X-1 is associated with the supernova remnant G321.9-0.3 then we find a limiting minimum age of this remnant of 60000 yr. Furthermore, we predict that the companion star has lost 10% of its mass as a result of stripping and ablation from the impact of the supernova shell shortly after the explosion

Modeling CCH Switch to SCH in IEEE 802.11p/WAVE Vehicular Networks

© 2017 IEEE. Packet collision and packet delay are considered to be critical for safety applications in vehicular networks. This paper designs a new analytical model to evaluate the performance of channel switching for IEEE 802.11p/WAVE in vehicular networks. Under this model, it explicitly expresses the WAVE channel switching, and constructs contention window size and number of vehicles as packet collision probability and packet delay time function of variables. Finally, we evaluate accuracy of the designed model of collision caused by channel switching and transmission delay in vehicular networks. The results show that the model could analyzes perfectly packet collision which is caused by channel switching and packet delay in vehicular networks

Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients

S-CKD602 is a PEGylated liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. The objective of this study was to characterize the bidirectional pharmacokinetic-pharmacodynamic (PK-PD) interaction between S-CKD602 and monocytes. Plasma concentrations of encapsulated CKD-602 and monocytes counts from 45 patients with solid tumors were collected following intravenous administration of S-CKD602 in the phase I study. The PK-PD models were developed and fit simultaneously to the PK-PD data, using NONMEM®. The monocytopenia after administration of S-CKD602 was described by direct toxicity to monocytes in a mechanism-based model, and by direct toxicity to progenitor cells in bone marrow in a myelosuppression-based model. The nonlinear PK disposition of S-CKD602 was described by linear degradation and irreversible binding to monocytes in the mechanism-based model, and Michaelis-Menten kinetics in the myelosuppression-based model. The mechanism-based PK-PD model characterized the nonlinear PK disposition, and the bidirectional PK-PD interaction between S-CKD602 and monocytes. © 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd

Recent Breakthroughs on Angle-of-Arrival Estimation for Millimeter-Wave High-Speed Railway Communication

© 2019 IEEE. With significantly improved efficiency, largescale hybrid antenna arrays with tens to hundreds of antennas have great potential to support millimeter-wave (mmWave) communication for high-speed railway (HSR) applications. The significant beamforming gains rely on fast and accurate estimation of the angle-of-arrival (AoA), but this can be impeded by the high train speed, the cost/energy oriented design of arrays, and the severe attenuation of mmWave signals. This article reviews these challenges, and discusses the limitations of existing AoA estimation techniques under hybrid antenna array settings. The article further reveals a few recent theoretical breakthroughs that can potentially enable fast and reliable estimation, even based on severely attenuated signals. Under a speed setting of 500 km/h, a performance study is carried out to confirm the significant improvements of estimation accuracy and subsequent beamforming gains as the results of the breakthroughs

Model Predictive Switching Pattern Control for Current-Source Converters with Space-Vector-Based Selective Harmonic Elimination

© 2017 IEEE. This paper presents a model predictive switching pattern control (MPSPC) for a current-source converter (CSC), which achieves superb low-order harmonics elimination performance in steady state and improved transient responses. Based on a proposed space-vector-based selective harmonic elimination (SHE) method and prediction of load current at the next sampling instant, MPSPC prefers to following a precalculated SHE-pulse width modulation (PWM) pattern in steady state, and governing the CSC through a model predictive control (MPC) approach during transients. In comparison with existing schemes, the advantages of MPSPC are threefold: First, quantization error, introduced by a constant sampling frequency in MPC and degrading steady-state low-order harmonic elimination, is mitigated in the proposed scheme. Second, there is no weighting factor in the cost function, as used in existing schemes. Finally, MPSPC is totally realized based on one-step prediction, which simplifies the structure of the scheme. Both simulation and experimental results verify the steady state and dynamic performance of MPSPC with different SHE-PWM patterns

Designed Dynamic Reference with Model Predictive Control for Bidirectional EV Chargers

© 2013 IEEE. This paper presents a finite control set model predictive control (MPC) using a designed dynamic reference for bidirectional electric vehicle (EV) chargers. In the conventional MPC scheme, a PI controller is involved to generate an active power reference from the DC voltage reference. It is hard to find one fixed set of coefficients for all working conditions. In this paper, a designed dynamic reference based MPC strategy is proposed to replace the PI control loop. In the proposed method, a DC voltage dynamic reference is developed to formulate the inherent relationship between the DC voltage reference and the active power reference. Multi-objective control can be achieved in the proposed scheme, including controlling of the DC voltage, battery charging/discharging current, active power and reactive power, independently. Bidirectional power flow is operated effectively between the EV- and the grid-side. Experimental results are obtained from a laboratory three-phase two-stage bidirectional EV charger controlled by dSPACE DS1104. The results show that fast dynamic and good steady state performance of tracking the above objectives can be achieved with the proposed method. Compared with the system performance obtained by the conventional MPC method, the proposed method generates less active power ripples and produces a better grid current performance

Evidence for vacuum birefringence from the first optical-polarimetry measurement of the isolated neutron star RX J1856.5−3754

The ‘Magnificent Seven’ (M7) are a group of radio-quiet isolated neutron stars discovered in the soft X-rays through their purely thermal surface emission. Owing to the large inferred magnetic fields (B ≈ 1013 G), radiation from these sources is expected to be substantially polarized, independently of the mechanism actually responsible for the thermal emission. A large observed polarization degree (PD) is, however, expected only if quantum-electrodynamic (QED) polarization effects are present in the magnetized vacuum around the star. The detection of a strong linearly polarized signal would therefore provide the first observational evidence of QED effects in the strong-field regime. While polarization measurements in the soft X-rays are not feasible yet, optical polarization measurements are within reach also for quite faint targets, like the M7 which have optical counterparts with magnitudes ≈26–28. Here, we report on the measurement of optical linear polarization for the prototype, and brightest member, of the class, RX J1856.5−3754 (V ∼ 25.5), the first ever for one of the M7, obtained with the Very Large Telescope. We measured a PD = 16.43 ± 5.26 per cent and a polarization position angle PA = 145°.39 ± 9°.44, computed east of the North Celestial Meridian. The PD that we derive is large enough to support the presence of vacuum birefringence, as predicted by QED

Predictive Control of Cascaded H-Bridge Converters under Unbalanced Power Generation

© 1982-2012 IEEE. This paper presents a predictive control strategy for grid-connected cascaded H-bridge (CHB) converters under unbalanced power generation among each converter phase. The proposed controller belongs to the finite-control-set model predictive control (FCS-MPC) family and is designed to extract unbalanced power from each CHB converter phase while providing balanced power to the grid. The key novelty of this strategy lies in the way the unbalanced power generation among the phases is explicitly considered into the optimal control problem. Power balance is achieved by enforcing the CHB converter to work with a suitable zero-sequence voltage component. The proposed predictive controller is directly formulated in the original abc-framework to account for the common-mode voltage. Simulation and experimental results are provided to verify the effectiveness of the proposed FCS-MPC strategy