Monolithic integration of power transistor and specific functional integrated circuits (power ICs) offers unique advantages for wide bandgap power devices. However, few publications have reported the ...power ICs based on SiC because of several challenging problems such as fabrication process and cost. This paper explores the monolithic integration possibility of 4H-SiC lateral small-signal bipolar junction transistors (BJTs) and vertical power BJT without extra mask or processing step other than Vanadium isolation implantation. A new monolithic power integration architecture is proposed and optimized using TCAD simulations first, and then both the vertical and lateral SiC BJT types are fabricated on the same wafer using the standard power BJT process to experimentally verify the feasibility of the monolithic integration method. The SiC power BJT demonstrates a breakdown voltage of 1320 V and a peak common-emitter current gain of 13.1 while the lateral SiC BJT demonstrated a breakdown voltage of 25 V and a peak common-emitter current gain of 3.8 at room temperature. While the device performance can be further improved, the fact that they can be successfully fabricated on the same wafer without much process modification shows a great promise of realizing monolithic SiC power ICs, which will greatly benefit the next-generation power electronics systems.
Zika virus (ZIKV) is an Aedes-mosquito-borne flavivirus that causes debilitating congenital and developmental disorders. Improved understanding of ZIKV pathogenesis could assist efforts to fill the ...therapeutic and vaccine gap. We use several ZIKV strains, including a pair differing by a single phenylalanine-to-leucine substitution (M-F37L) in the membrane (M) protein, coupled with unbiased genomics to demarcate the border between attenuated and pathogenic infection. We identify infection-induced metabolic dysregulation as a minimal set of host alterations that differentiates attenuated from pathogenic ZIKV strains. Glycolytic rewiring results in impaired oxidative phosphorylation and mitochondrial dysfunction that trigger inflammation and apoptosis in pathogenic but not attenuated ZIKV strains. Critically, pyruvate supplementation prevents cell death, in vitro, and rescues fetal development in ZIKV-infected dams. Our findings thus demonstrate dysregulated metabolism as an underpinning of ZIKV pathogenicity and raise the potential of pyruvate supplementation in expectant women as a prophylaxis against congenital Zika syndrome.
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•Metabolic dysregulation delimits attenuated and pathogenic Zika virus (ZIKV) infections•Pathogenic ZIKV infection diverts glycolytic carbon into the pentose phosphate pathway•Compromised oxidative phosphorylation leads to mitochondrial stress and cell death•Pyruvate supplementation alleviates ZIKV pathogenesis in a congenital mouse model
In this study, Yau et al. demarcate the border between attenuated and pathogenic Zika virus infections, demonstrating that metabolic dysregulation is an underpinning of congenital disease. The authors also demonstrate that ethyl pyruvate supplementation alleviates Zika virus pathogenesis in a congenital mouse model, highlighting a potential therapeutic option for development.
Planar split‐gate MOSFETs (SG‐MOSFETs) are promising in high‐frequency power applications due to the fast turn on/off speeds and low switching loss. However, SG‐MOSFETs suffer from crowded electric ...field at the edge of the split poly‐Si gate, resulting in the degradation of the blocking voltage and the gate oxide reliability. This issue becomes more critical in 4H‐SiC MOSFETs due to the high critical breakdown electric field. In this work, a new 1.2‐kV 4H‐SiC SG‐MOSFET structure is proposed and investigated by TCAD simulation. The proposed structure features a source metal field plate located between two adjacent split poly‐Si gates (termed SFP‐SG‐MOSFET). In the blocking state, the source metal field plate reduces the peak electric field at the edge of the poly‐Si gate. The maximum electric field in the gate oxide of the proposed SFP‐SG‐MOSFET is reduced by 52.8% compared with the SG‐MOSFET, for reliable operation. The reverse transfer capacitance (Crss) and gate‐to‐drain charge (Qgd) are reduced by 56.4% and 61.8% compared with SG‐MOSFETs, respectively. Therefore, the high‐frequency figure‐of‐merits (HF‐FOM) Ron × Crss and Ron × Qgd are improved by 2.2 times and 2.5 times, respectively.
13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China based on immunologic noninferiority to 7-valent PCV (PCV7). As part of the noninferiority study, immunogenicity and safety of ...PCV13 administered as a 3- or 2-dose infant series followed by a toddler dose were examined in healthy Chinese infants.
Infants (42- to 77-days-old) were randomized to a 3-dose PCV13 or PCV7 infant series administered double-blind at 3, 4 and 5 months or PCV13 administered open-label at 2, 4 and 6 months and a 2-dose open-label series at 3 and 5 months; all subjects received a toddler dose (12 months). Serotype-specific immunoglobulin G (IgG) concentrations were measured 1 month after the infant series and before and after the toddler dose. Opsonophagocytic activity (OPA) was measured in a subset of subjects at each time point. Safety was evaluated.
One month after the infant series, serotype-specific immune responses (IgG ≥ 0.35 µg/mL) were similar for the 2- versus 3-dose schedules, except for serotype 6B, which was significantly lower in the 2-dose group 70.1% in the PCV13 (3, 5 + 12 mo) group vs. 93.2% in the PCV13 (3, 4, 5 + 12 mo) group and 94.7% in the PCV13 (2, 4, 6 + 12 mo) group. IgG geometric mean concentrations and OPA geometric mean titers trended numerically higher with 3- versus 2-dose schedules. No significant differences in immunogenicity were observed between the 3- versus 2-dose schedules after the toddler dose. PCV13 was well-tolerated across all schedules.
PCV13 administered as a 3- or 2-dose infant series followed by a toddler dose was immunogenic and well tolerated in healthy Chinese infants and likely protective against PCV13 serotypes; immune responses with a 2-dose schedule were lower for some serotypes.
SiC bipolar junction transistor (BJT) still offers an attractive alternative to the more popular SiC MOSFET because of its several advantages, such as low fabrication cost, fast switching speed, and ...high temperature durability. However, it has not been widely accepted in the market partially because the large constant base current induces large power consumption on its base driver during on-state. In this paper, a new proportional base driver is proposed to provide adaptive base current for SiC BJT and thus minimize its driver power consumption when operating within a wide range of load current and operation temperature in SiC BJT-based power converters. It simply uses a silicon BJT serially connected with a current sensor as a current-/temperature-controlled current source in the base driver circuit, promptly supplying adaptive base current for SiC BJT whenever the SiC BJT's junction temperature and/or operation current varies. The operation principle of this proportional base driver is theoretically analyzed and then experimentally verified in a 600-V/20-A SiC BJT-based dc/dc boost converter. Experimental results show that the proposed proportional base driver is capable of driving the SiC BJT much more efficiently than the GeneSiC's constant base driver, greatly reducing the power consumption of base driver by more than 50% over wide ranges of operation currents and temperatures.
Monolithic integration of antiparallel diode with power transistor offers unique advantages for wide bandgap (WBG) power devices. However, the blocking voltage degradation issue stands in the way in ...the development of the integrated devices. This paper presents the design, fabrication, and verification of a monolithically integrated SiC BJT and antiparalleled junction barrier Schottky (JBS) diode (BJT/JBS), which has achieved a blocking voltage very close to that of the individual transistor or diode. It introduces isolation rings into the border region, separating the transistor and diode. The design was first validated successfully by TCAD simulations, and then some integrated device samples were fabricated to experimentally verify the feasibility of the isolation rings in improving their blocking voltages. Besides, the fabrication of the 4H-SiC-integrated BJT/JBS switch adopted a single metal, single thermal treatment process to form ohmic contacts on p + regions and Schottky contacts on the N-epilayer simultaneously. Hence, there was not any additional step added to the SiC BJT baseline process. A breakdown voltage of 1340 V at a leakage current of 10 <inline-formula> <tex-math notation="LaTeX">\mu \text{A} </tex-math></inline-formula> is experimentally observed, and the simulation results and design optimization are discussed.
•PCV13 is currently provided in SDS which has implications for cold chain requirements.•PCV13 in a multidose vial (MDV) is formulated with the preservative 2-phenoxyethanol.•Comparison of safety and ...immunogenicity of MDV with SDS was therefore required.•MDV was found safe and noninferior to SDS for all 13 pneumococcal serotypes.•PCV13 MDV can help optimize vaccination in resource-limited settings.
This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS).
Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity (OPA; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than −10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected.
500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups.
PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.
How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. ...GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.
A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5.
Highlights • In a previous study, Chinese infants were vaccinated with PCV7, PCV7 + DTaP, or DTaP. • Antibody persistence was assessed at a single time point 3 years after last dose. • After 3 years, ...serum IgG had declined but remained higher than before vaccination. • PCV7 serospecific antibodies were generally similar after PCV7 and PCV7 + DTaP. • Protective immunity was not influenced by the concomitant administration of DTaP.
Six new coordination polymers, namely, Pb(L)(H2O) (1), Pb(L)(phen) (2), Pb2(L)2(4,4′-bipy)0.5 (3), Cd(L)(phen) (4), Cd(L)(4,4′-bipy)·H2O (5) and Mn(L)(4,4′-bipy)·H2O (6) have been synthesized by the ...hydrothermal reaction of 2,2′-hexafluoroisopropylidenebis(p-phenyleneoxy)diacetic acid (H2L) with Pb(II)/Cd(II)/Mn(II) in the presence of ancillary ligands 4,4′-bipyridine (4,4′-bipy) or 1,10-phenanthroline (phen). Complexes 1 and 4–6 exhibit 2-D structures, and complexes 2–3 display 3-D frameworks, of which L2− ligands join metal ions to single-stranded helical chains of 1, 3–6 and double-stranded helical chains of 2. Complexes 2 and 3 also contain double-stranded Metal–O helices. Topology analysis reveals that complexes 1 and 4 both represent 4-connected sql net, 2 represents 6-connected pcu net, 3 exhibits a novel (3,12)-connected net, while 5 and 6 display (3,5)-connected gek1 net. The six complexes exhibit two kinds of inorganic–organic connectivities: I0O2 for 1, 4–6, and I1O2 for 2–3. The photoluminescent properties of 4–5 and the magnetic properties of 6 have been investigated.
Six new Pb(II)/Cd(II)/Mn(II) coordination polymers with helical structures based on flexible V-shaped dicarboxylate ligand have been synthesized and structurally characterized. Photoluminescent and magnetic properties have been investigated. Display omitted
•Six novel M(II) coordination polymers with 2,2′-hexafluoroisopropylidenebis(p-phenyleneoxy)diacetic acid and N-donor ligands.•Complexes 1–6 show diverse intriguing helical characters.•The luminescent properties of complexes 1–5 were investigated.•Complex 6 shows antiferromagnetic coupling.
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