Summary Background Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte ...stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group BILAG A organ domain score and no more than 1 new B organ domain score; and no worsening <0·3 increase in Physician's Global Assessment PGA score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00424476. Findings 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 51%, odds ratio 1·55 95% CI 1·10–2·19; p=0·0129) and 10 mg/kg (167 58%, 1·83 1·30–2·59; p=0·0006) than with placebo (125 44%) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 53%, 1·51 1·07–2·14; p=0·0189) and 10 mg/kg (169 58%, 1·71 1·21–2·41; p=0·0024) than with placebo (132 46%). More patients given belimumab 1 mg/kg (226 78%, 1·38 0·93–2·04; p=0·1064) and 10 mg/kg (236 81%, 1·62 1·09–2·42; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 73%). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 79%, 1·68 1·15–2·47; p=0·0078) and 10 mg/kg (231 80%, 1·74 1·18–2·55; p=0·0048) than with placebo (199 69%). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding Human Genome Sciences and GlaxoSmithKline.
It is highly desirable to monolithically integrate a high-performance freewheeling diode (FWD) in both Si and SiC power MOSFETs for power electronic applications. This is especially true for a SiC ...MOSFET since its inherent body diode has a very large turn-on knee voltage (~2.7 V). The purpose of this numerical study is to investigate a new 1200 V SiC MOSFET structure with an integrated heterojunction diode formed between n-type polysilicon and n-type SiC (termed HJD-MOSFET). The proposed HJD-MOSFET uses a mesa structure to accommodate the heterojunction FWD without sacrificing any active area while leaving the split-gate planar MOSFET cells in the trench. A p-shield region surrounding the heterojunction, along with the p-base of the MOS cells, shields high electric fields and maintains a high breakdown voltage. Three key HJD-MOSFET device parameters are identified and optimized in this article. The HJD-MOSFET offers a turn-on knee voltage of 0.5 V, roughly five times lower than the intrinsic SiC body diode or two times lower than a typical SiC Schottky barrier diode due to the low barrier height of the n/n heterojunction (~0.68 eV). Finally, the gate charge of HJD-MOSFET is reduced by 42% compared with conventional MOSFET since the poly-Si gate electrode is significantly reduced to accommodate the heterojunction FWD.
Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold ...BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6%∼96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
The 1.2-kV-rated 4H-SiC planar split-gate (SG) MOSFET embedding source field plate incorporated between separated gates (termed SFP-SG-MOSFET) is proposed and demonstrated. The utilization of the ...embedding source field plate in conventional SG-MOSFET (Conv-SG-MOSFETs) serves to alleviate the adverse effects of electric field crowding. It also maintains the minimum reverse transfer capacitance (<inline-formula> <tex-math notation="LaTeX">\textit{C}_{\text{rss}}\text{)}</tex-math> </inline-formula>. As a result, the high-frequency figure-of-merit (HF-FOM) and switching efficiency of the proposed SFP-SG MOSFET are improved compared to those of a conventional planar-gate MOSFET (Conv-PG-MOSFET) while maintaining the same blocking voltage rating. The experimental results demonstrate that <inline-formula> <tex-math notation="LaTeX">\textit{C}_{\text{rss}}</tex-math> </inline-formula> of the fabricated devices is reduced by 80% and 53% at <inline-formula> <tex-math notation="LaTeX">\textit{V}_{\text{ds}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">=</tex-math> </inline-formula> 0 V and <inline-formula> <tex-math notation="LaTeX">\textit{V}_{\text{ds}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">=</tex-math> </inline-formula> 800 V, respectively. Thus, the SFP-SG-MOSFET exhibits HF-FOMs <inline-formula> <tex-math notation="LaTeX"><</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">\textit{R}_{\text{ON}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">\times</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">\textit{C}_{\text{rss}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">></tex-math> </inline-formula> 4.9 times lower at <inline-formula> <tex-math notation="LaTeX">\textit{V}_{\text{ds}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">=</tex-math> </inline-formula> 0 V and 2.0 times lower at <inline-formula> <tex-math notation="LaTeX">\textit{V}_{\text{ds}}</tex-math> </inline-formula> <inline-formula> <tex-math notation="LaTeX">=</tex-math> </inline-formula> 800 V. Furthermore, the switching loss of the SFP-SG-MOSFET is reduced by 25%. This makes it possible for the proposed devices to handle a higher power density.
Thanks to its fast self-synchronization capability, the virtual oscillator control (VOC) has become an emerging control technique for grid-connected inverters, especially in single-phase ...applications. Nevertheless, the nonlinearity of VOC inverters impacts its dynamic behavior, and there is a trade-off between the system stability and accurate power regulation in VOC-based microgrids. This paper studies the dynamic stability of VOC inverters for guiding the parameter design. Then, based on the analysis result, an improved VOC strategy with hybrid power regulation structure is proposed for improving both the system stability and power regulation of VOC-based microgrids. First, a dynamic phasor (DP) model of single-phase VOC-based microgrids with multiple control loops is developed. Second, a stability region analysis of VOC parameters is performed, the proper mode setting and robust parameter design of VOC inverters are provided. Third, the improved VOC strategy is presented, achieving accurate power sharing, fast voltage recovery and adequate stability margin. The proposed parameter design and improved VOC strategy are validated by simulation and hardware-in the-loop experiment.
Monolithic integration of junction barrier-controlled Schottky (JBS) diode with SiC MOSFET (termed JMOS) offers unique advantages. However, the short-circuit (SC) ruggedness issue stands in the way ...of the development of the conventional JMOS. The purpose of this numerical study is to investigate a new 4H-SiC JMOS with a self-pinching (SP) structure formed in the JFET region (termed SP-JMOS). The SP structure features that an N-type current spread layer is sandwiched between the P+ layer and the buried P-shield layer, forming a lateral JFET channel. In the forward conduction state, the lateral JFET channel self-pinches off and clamps the potential, thus limiting the saturation current of the device. In the blocking state, both the P+ layer and the buried P-shield layer collaboratively shield the Schottky contact and the SiC/SiO 2 interface from a high electric field for long-term reliable operation. Numerical simulation results show that the proposed SP-JMOS not only withstands a roughly <inline-formula> <tex-math notation="LaTeX">2.6\times </tex-math></inline-formula> longer SC withstanding time than that of the conventional JMOS, but also shows an ultralow oxide electric field in the SP-JMOS.
The complex allotetraploid nature of the cotton genome (AADD; 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled the Gossypium arboreum ...(AA; 2n = 26) genome, a putative contributor of the A subgenome. A total of 193.6 Gb of clean sequence covering the genome by 112.6-fold was obtained by paired-end sequencing. We further anchored and oriented 90.4% of the assembly on 13 pseudochromosomes and found that 68.5% of the genome is occupied by repetitive DNA sequences. We predicted 41,330 protein-coding genes in G. arboreum. Two whole-genome duplications were shared by G. arboreum and Gossypium raimondii before speciation. Insertions of long terminal repeats in the past 5 million years are responsible for the twofold difference in the sizes of these genomes. Comparative transcriptome studies showed the key role of the nucleotide binding site (NBS)-encoding gene family in resistance to Verticillium dahliae and the involvement of ethylene in the development of cotton fiber cells.
The fast turn-on speed of silicon carbide (SiC) gate-turn-off (GTO) thyristor is preferred for pulse power applications. However, the turn-on delay phenomenon hinders its improvement. In this ...article, the dynamic turn-on transient process of SiC GTO thyristor is investigated and analyzed extensively by means of both numerical simulation and physical modeling. The physical mechanism behind its turn-on transient process is discussed in detail. A physical model based on the charge-control theory is proposed to identify the dominant factors influencing the dynamic turn-on transient. Then the theoretical analysis is quantitatively made on the parameter design of GTO's unit cell, and methods to increase the turn-on switch speed are extensively discussed. This study provides not only in-depth physical insights into the device's turn-on characteristics, but also designs guidelines for the advancement of SiC GTO thyristor.
The Smart Discrete concept which monolithically integrates a vertical high-voltage power device with low-voltage smart circuits has been widely adopted in silicon world for many years and may bring ...similar benefits to SiC world. For example, it is highly desirable to integrate a gate driver circuit onto a high-voltage SiC thyristor for ultra-fast turn-on. However, the electrical isolation between the vertical high-voltage power device and the low-voltage circuit elements remains a major technical challenge for silicon, and even more so for SiC due to the very limited processing options. In this article, we propose a combination of shallow junction isolation (JI) and partial dielectric isolation (DI) for high-voltage 4H-SiC smart thyristor, which is monolithically integrated with low-voltage nMESFET circuits. The characterization of fabricated devices and analysis of leakage currents across the isolation structure have been done to experimentally verify the feasibility of the isolation method. 8 V parasitic lateral NPNP thyristor between a 6.3 kV 4H-SiC thyristor and isolation moats, 175 V lateral PNP transistor between the passive resistor and isolation moats, and 10 V lateral reverse-biased p-n diode between nMESFET and isolation moats are experimentally demonstrated.
The SiC bipolar junction transistor (BJT) offers an attractive alternative to the more popular SiC mosfet . It is important to develop an accurate SPICE model for the SiC BJT to enable its use in ...power electronic applications. The current gain of an SiC BJT may degrade considerably at high current levels and/or at high temperatures largely due to the surface recombination effect. In this paper, an improved SPICE behavioral model that accurately accounts for the current gain depending on the collector current and the junction temperature is proposed for the SiC BJT. In this paper, the conventional Gummel-Poon model is extended to include this important physical effect by adding a diode between the external base and emitter terminals of the BJT. A two-step model parameter extraction method is developed. First, the basic Gummel-Poon model parameters are extracted from low-current measurement data, and then, the new surface recombination model parameters are extracted by observing the difference between the measured high-level base current and the standard Gummel-Poon model prediction. The simulated static and switching characteristics of the new SiC BJT model match the measured data very well. Finally, the new SPICE model is used in the performance assessment of a proportional base driver technique embedded in a 3.6-kW boost converter, demonstrating its validity in helping with the optimum design of power electronic applications based on SiC BJTs.
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