Insulated gate and surface passivation structures for GaN-based power transistors

Recent years have witnessed GaN-based devices delivering their promise of unprecedented power and frequency levels and demonstrating their capability as an able replacement for Si-based devices. High-electron-mobility transistors (HEMTs), a key representative architecture of GaN-based devices, are well-suited for high-power and high frequency device applications, owing to highly desirable III-nitride physical properties. However, these devices are still hounded by issues not previously encountered in their more established Si- and GaAs-based devices counterparts. Metal–insulator–semiconductor (MIS) structures are usually employed with varying degrees of success in sidestepping the major problematic issues such as excessive leakage current and current instability. While different insulator materials have been applied to GaN-based transistors, the properties of insulator/III-N interfaces are still not fully understood. This is mainly due to the difficulty of characterizing insulator/AlGaN interfaces in a MIS HEMT because of the two resulting interfaces: insulator/AlGaN and AlGaN/GaN, making the potential modulation rather complicated. Although there have been many reports of low interface-trap densities in HEMT MIS capacitors, several papers have incorrectly evaluated their capacitance–voltage (C–V) characteristics. A HEMT MIS structure typically shows a 2-step C–V behavior. However, several groups reported C–V curves without the characteristic step at the forward bias regime, which is likely to the high-density states at the insulator/AlGaN interface impeding the potential control of the AlGaN surface by the gate bias. In this review paper, first we describe critical issues and problems including leakage current, current collapse and threshold voltage instability in AlGaN/GaN HEMTs. Then we present interface properties, focusing on interface states, of GaN MIS systems using oxides, nitrides and high-κ dielectrics. Next, the properties of a variety of AlGaN/GaN MIS structures as well as different characterization methods, including our own photo-assisted C–V technique, essential for understanding and developing successful surface passivation and interface control schemes, are given in the subsequent section. Finally we highlight the important progress in GaN MIS interfaces that have recently pushed the frontier of nitride-based device technology

Detection of drug-sensitizing EGFR exon 19 deletion mutations in salivary gland carcinoma

Activating mutations within the epidermal growth factor receptor (EGFR) identify lung adenocarcinoma patients with improved clinical responses to tyrosine kinase inhibitors gefitinib and erlotinib. By screening salivary gland carcinoma, two drug-sensitizing EGFR exon 19 delE746-A750 mutations were identified in an adenocystic and in a mucoepidermoid carcinoma of the parotid gland

Using DNA Methylation Patterns to Infer Tumor Ancestry

Background: Exactly how human tumors grow is uncertain because serial observations are impractical. One approach to reconstruct the histories of individual human cancers is to analyze the current genomic variation between its cells. The greater the variations, on average, the greater the time since the last clonal evolution cycle (‘‘a molecular clock hypothesis’’). Here we analyze passenger DNA methylation patterns from opposite sides of 12 primary human colorectal cancers (CRCs) to evaluate whether the variation (pairwise distances between epialleles) is consistent with a single clonal expansion after transformation. Methodology/Principal Findings: Data from 12 primary CRCs are compared to epigenomic data simulated under a single clonal expansion for a variety of possible growth scenarios. We find that for many different growth rates, a single clonal expansion can explain the population variation in 11 out of 12 CRCs. In eight CRCs, the cells from different glands are all equally distantly related, and cells sampled from the same tumor half appear no more closely related than cells sampled from opposite tumor halves. In these tumors, growth appears consistent with a single ‘‘symmetric’ ’ clonal expansion. In three CRCs, the variation in epigenetic distances was different between sides, but this asymmetry could be explained by a single clonal expansion with one region of a tumor having undergone more cell division than the other. The variation in one CRC was complex and inconsistent with a simple single clonal expansion

Allelic losses on chromosome 3p are accumulated in relation to morphological changes of lung adenocarcinoma

We performed allelotyping analysis at nine regions on chromosome 3p using 56 microdissected samples from 23 primary lung adenocarcinomas to examine the process of progression within individual lung adenocarcinoma with various grades of differentiation. Identical allelic patterns among various grades of differentiation were found in eight cases. Accumulation of allelic losses from high to lower differentiated portions was found in seven cases and accumulation of allelic losses from low to higher differentiated portions was found in five cases. Various allelic patterns among various grades of differentiation were found in three cases. These results suggested that allelic losses on 3p play an important role in morphological changes of lung adenocarcinomas. We also investigated the relationship between allelic losses on 3p and histological subtypes of lung adenocarcinoma. The frequencies of allelic losses at 3p14.2 and telomeric region of 3p21.3 were higher in papillary type tumour (nine out of 14, 64% and 11 out of 15, 73%) than in bronchioloalveolar carcinoma-type tumour (one out of 8, 13%; P=0.031 and four out of 12, 33%; P = 0.057). These results indicated that allelic losses at 3p14.2 and telomeric region of 3p21.3 are related to pattern of the proliferation of lung adenocarcinoma

Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

This study investigated the relation between positive thyroid transcription factor 1 (TTF1) staining and survival of patients affected by primary adenocarcinoma (ADC) of the lung. Pathological tissue from consecutive ADC patients was collected from 2002 to 2004. The anti-TTF1 antibody (8G7G3/1, dilution of 1/200) was used. Thyroid transcription factor 1 staining was assessed for each tumour as positive or negative. Probability of survival was estimated by Kaplan–Meier and difference tested by log-rank test. A Cox's regression multivariate analysis was carried out. In all, 106 patients were studied (66% male, 69% PS0–1, 83% with stage III or IV). Tumours expressed positive TTF1 staining in 66% of cases. Multivariate analysis demonstrated an independent lower risk of death for patients whose tumour expresses positive TTF1 staining (HR=0.51, 95% CI 0.30–0.85; P=0.01) and higher grade of differentiation (HR=0.40, 95% CI 0.24–0.68; P=0.001). In conclusion, positive TTF1 staining strongly and independently correlates with survival of patients with primary ADC of the lung

Tracing ancestry with methylation patterns: most crypts appear distantly related in normal adult human colon

BACKGROUND: The ability to discern ancestral relationships between individual human colon crypts is limited. Widely separated crypts likely trace their common ancestors to a time around birth, but closely spaced adult crypts may share more recent common ancestors if they frequently divide by fission to form clonal patches. Alternatively, adult crypts may be long-lived structures that infrequently divide or die. METHODS: Methylation patterns (the 5' to 3' order of methylation) at CpG sites that exhibit random changes with aging were measured from isolated crypts by bisulfite genomic sequencing. This epigenetic drift may be used to infer ancestry because recently related crypts should have similar methylation patterns. RESULTS: Methylation patterns were different between widely separated ("unrelated") crypts greater than 15 cm apart. Evidence for a more recent relationship between directly adjacent or branched crypts could not be found because their methylation pattern distances were not significantly different than widely separated crypt pairs. Methylation patterns are essentially equally different between two adult human crypts regardless of their relative locations. CONCLUSIONS: Methylation patterns appear to record somatic cell trees. Starting from a single cell at conception, sequences replicate and may drift apart. Most adult human colon crypts appear to be long-lived structures that become mosaic with respect to methylation during aging

Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations

Division of Medical Oncology and Surgical Oncolog