Degradation mechanism of Schottky diodes on inductively coupled plasma-etched n-type 4H-SiC

The degradation mechanism of Ta Schottky contact on 4H-SiC exposed to an inductively coupled plasma (ICP) was studied using deep-level transient spectroscopy and angle-resolved x-ray photoelectron spectroscopy (XPS). Four kinds of traps T1, T2, T3, and T4 were observed in the ICP-etched sample. The T4 trap was deep in the bulk, but the shallower levels, T1, T2 and T3, were localized near the contact. From angle-resolved XPS measurements, the ICP-etched surface was found to be carbon deficient, meaning the production of carbon vacancies by ICP etching. The activation energies 0.48 (T3 trap) and 0.60 eV (T4 trap) agreed well with the previously proposed energy level of V-C (0.5 eV). The ICP-induced traps provided a path for the transport of electrons at the interface of metal with Sic, leading to a reduction of the Schottky barrier height and an increase of the gate leakage current.open6

The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1

Gemcitabine is used to treat several cancers including lung cancer. However, tumor cells often escape gemcitabine-induced cell death via various mechanisms, which include modulating bcl-2 family members and NF-κB activation. We previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is sufficient to induce apoptosis in 293T cells. In the present study, we investigated the anti-tumor effect of combined BC gene therapy and gemcitabine chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40 ng/ml), which induced NF-κB activation and concomitant up-regulation of Bfl-1 (an NF-κB-regulated anti-apoptotic protein). BC induced the apoptosis of A549 and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and low dose gemcitabine synergistically and efficiently induced mitochondria-mediated apoptosis in these cells. When administered alone or with low dose gemcitabine, BC suppressed NF-κB activity, inhibited the nuclear translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore, direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine-induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest that lung cancer cells become resistant to gemcitabine via NF-κB activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-κB inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer

Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea

Background Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. Methods The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. Results During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU– phenotype, followed by eGFRnorPU+ and eGFRnorPU–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU–. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU– to PU+ showed a higher risk of HHF than those who converted from PU+ to PU–. Conclusion Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM

Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study

Introduction: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.Methods: All 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4_89, padi4_90, and padi4_92) and one synonymous (padi4_104) singlenucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI).Results: A functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms.Conclusions: A haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contri bution is affected by gene-gene interactions with HLADRB1 SE alleles.We are grateful to many research workers for assistance with sample preparation, data collection, and technical study. Dr. Bang&#39;s work was supported by a grant from the Korea Healthcare Technology R&amp;D Project (A090706). Dr. Bae&#39;s work was supported by a grant from the Korea Healthcare Technology R&amp;D Project (A084794 and A010252). Dr. Kang&#39;s work was supported by a grant from the Research Program for New Drug Target Discovery (M10748000231-08N4800-23110)

YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration.

Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, damage-associated transient progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this stepwise mapping to cell fate transitions shows how an inflammatory niche controls alveolar regeneration by controlling stem cell fate and behavior.We would like to thank Emma Rawlins (University of Cambridge, UK) for valuable scientific discussions and sharing the mouse lines; We would like to thank Randall Johnson (University of Cambridge, UK) for sharing Hif1aflox/flox mouse line; Nisha Narayan and Brian Huntly for sharing materials and discussion on glycolysis experiments; Irina Pshenichnaya (Histology), Maike Paramor (NGS library), Peter Humphreys (Imaging), Andy Riddell (Flow cytometry), Simon McCallum (Flow cytometry, Cambridge NIHR BRC Cell Phenotyping Hub), Katarzyna Kania (single cell sequencing at Cancer Research UK), and Cambridge Stem Cell Institute core facilities for technical assistance; Papworth Hospital Research Tissue Bank for providing tissue samples from IPF and lung adenocarcinoma (T02233); Kelly Evans for sharing histology samples of human lung tissue samples; Seungmin Han and Woochang Hwang for discussion on the scRNA-seq analysis; Life Science Editors for editorial assistance; All Lee Lab members for helpful discussion. This work was supported by Wellcome and the Royal Society (107633/Z/15/Z) and European Research Council Starting Grant (679411). J.C. was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03005399)

Electrical characteristics of metal-insulator-semiconductor Schottky diodes using a photowashing treatment in AlzGa1-xAs/InGaAs (X=0.75) pseudimorphic high electron mobility transistors

MIS Schottky diodes on Al0.75Ga0.25As/In0.2Ga0.8As PHEMTs were produced using both photowashing and H2O2 treatments. The Schottky contact on the GaAs layer with photowashing and H2O2 treatments showed enhancements of the SBH of about 0.11 and 0.05 eV, respectively. However, on the undoped AlGaAs layer, no further improvement in SBH was observed. After the photowashing treatment, the Ga oxide (Ga2O3) was dominantly created. In the mean time, two types of As oxide (As2O3,As5O2) were mainly produced by the H2O2 treatment, which are distributed uniformly on the GaAs surface. The thickness of the oxide layer formed by both treatments was nearly the same. Applying a representative model, formation of Ga oxide after the photowashing treatment effectively enhanced the SBH.open4