Back-end of line compatible transistors for hybrid CMOS applications

The low-temperature back-end of line (BEOL) compatible transparent amorphous oxide semiconductor (TAOS) TFTs and poly-Si TFTs are the suitable platforms for three-dimensional (3D) integration hybrid CMOS technologies. The n-channel amorphous indium tungsten oxide (a-IWO) ultra-thin-film transistors (UTFTs) have been successfully fabricated and demonstrated in the category of indium oxide based thin film transistors (TFTs). We have scaled down thickness of a-IWO channel to 4nm. The proposed a-IWO UTFTs with low operation voltages exhibit good electrical characteristics: near ideal subthreshold swing (S.S.) ~ 63mV/dec., high field-effect mobility (FE) ~ 25.3 cm2/V-s. In addition, we also have fabricated the novel less metal contamination Ni-induced lateral crystallization (LC-NILC) p-channel poly-Si TFTs. The matched electrical characteristics of n-channel and p-channel devices with low operation voltage and low IOFF are exhibiting the promising candidate for future hybrid CMOS applications

Tri-layer self-aligned structure indium gallium zinc oxide thin film transistor with optical synaptic plasticity

Since the 1950s, computer computing has been governed by the von Neumann architecture, which allows data to be transmitted across the processor and memory for computation. Nowadays, the demand for large amounts of information transmission has limited the processing speed by the memory bandwidth and generated higher power consumption. The Human brain can perform high-speed operation, store and calculate as one, so the human neuromorphic computation is the next-generation architecture to solve the “von Neumann bottleneck” [1- 2]. In this work, we have successfully developed tri-layer self-aligned structure indium gallium oxide (IGZO) thinfilm transistors (TFTs) with optical-synaptic plasticity. The channel conductance of IGZO TFTs would be modulated after the pulse voltage input from gate electrode. Please click Download on the upper right corner to see the full abstract

GAP-type low-temperature polycrystalline silicon thin film transistors for light sensing photo-transistor application

Recently, ultra-high resolution with biometric recognitions such as fingerprint sensing has been a major trend throughout the whole display industry. In order to meet the needs of high screen ratio, high sensitivity to read out, low temperature polycrystalline silicon (LTPS) thin film transistor (TFT) is considered one of the candidates for sensing application. Unlike photodiode, LTPS photo-transistor structured as transistor makes it possible to sensing under different region (off-state or on state) with relatively small sensing area. Please click Download on the upper right corner to see the full abstract

Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres. Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The impact of malnutritional status on survival in elderly hemodialysis patients

Background: The number of geriatric patients with end-stage renal disease undergoing maintenance hemodialysis has increased in Taiwan. However, protein-energy wasting is prevalent and associated with poor outcome in this patient population. It is generally well-known that geriatric nutritional risk index (GNRI) is a good survival predictor in general elderly patients. However, the association of GNRI with mortality in geriatric end-stage renal disease patients remains unclear. The present study aimed to assess the predictive ability of GNRI for overall mortality in elderly hemodialysis patients. Methods: GNRI was measured in a cohort of 104 hemodialysis patients aged ≥65 years. Thereafter, these patients were followed for a median period of 38.5 months. For all cases, all-cause mortality was the primary endpoint. Results: Patients with baseline GNRI <92 had significantly lower body weight, body mass index, serum albumin, and hemoglobin level, but were administered a higher erythropoietin dose as compared to those with GNRI ≥92. Basal GNRI independently correlated with erythropoietin resistance index (β = −1.97, p < 0.001) and serum high-sensitivity C-reactive protein (β = −0.71, p = 0.021). By the conclusion of the study, 45 patients had died. High GNRI was associated with the lower risk of mortality after adjustment for other potential confounders [hazard ratio = 0.41; 95% confidence interval (CI) = 0.22–0.90; p = 0.005]. Conclusion: GNRI is a significant predictor for mortality in elderly hemodialysis patients, and may be adopted to improve assessment of the malnutrition–inflammation status

Numerical Analysis of Oxygen-Related Defects in Amorphous In-W-O Nanosheet Thin-Film Transistor

The integration of 4 nm thick amorphous indium tungsten oxide (a-IWO) and a hafnium oxide (HfO2) high-κ gate dielectric has been demonstrated previously as one of promising amorphous oxide semiconductor (AOS) thin-film transistors (TFTs). In this study, the more positive threshold voltage shift (∆VTH) and reduced ION were observed when increasing the oxygen ratio during a-IWO deposition. Through simple material measurements and Technology Computer Aided Design (TCAD) analysis, the distinct correlation between different chemical species and the corresponding bulk and interface density of states (DOS) parameters were systematically deduced, validating the proposed physical mechanisms with a quantum model for a-IWO nanosheet TFT. The effects of oxygen flow on oxygen interstitial (Oi) defects were numerically proved for modulating bulk dopant concentration Nd and interface density of Gaussian acceptor trap NGA at the front channel, significantly dominating the transfer characteristics of a-IWO TFT. Furthermore, based on the studies of density functional theory (DFT) for the correlation between formation energy Ef of Oi defect and Fermi level (EF) position, we propose a numerical methodology for monitoring the possible concentration distribution of Oi as a function of a bias condition for AOS TFTs