Circular Capacitance Micromachined Ultrasonic Transducer

Capacitance micromachined ultrasonic transducers (CMUTs) have become an attractive alternative to the piezoelectric transducers, especially in air-coupled nondestructive evaluation (NDE) and ultrasound medical imaging flow metering,  micro/nanoelectronics, and industrial cleaning, etc. These are similar to other capacitance transducers as these employ a vibrating membrane to send and receive ultrasound in air and water. This paper describes the theory and design of a circular micromachined ultrasonic transducer which could lead to a CMUT with many advantages, including less loading effect. The software programs (Intellisuite 8.2 and MATLAB 7.0) were used to model a single cell of CMUT. The simulations-based studies of the critical parameters like collapse voltage and snapback voltage, which influence the operation of the CMUTs to a large extent, has been discussed. Small signal equivalent circuit model for the circular CMUT has been discussed and the program (SPICE) has been used for the simulation of the small signal equivalent circuit.Defence Science Journal, 2009, 59(6), pp.627-633, DOI:http://dx.doi.org/10.14429/dsj.59.156

Wnt/beta-catenin pathway: modulating anticancer immune response

Abstract Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway

Characterization of KRAS mutations (mt) in non-small cell lung cancer (NSCLC)

9544 Background: KRAS is the most commonly mutated oncogene in NSCLC and the development of direct KRAS inhibitors has renewed interest in this molecular subtype. However, there are several different KRAS mts, representing unique biology and different prognostic and therapeutic impact. A more comprehensive understanding of the genomic landscape relative to each KRAS mt subset will help guide therapeutic development. Methods: Molecular profiles of 17,113 NSCLC specimens were obtained using next-generation sequencing of 592 genes (Caris Life Sciences) and classified based on presence and types of KRAS mt. Incidence of KRAS mts was noted across the cohort and by histology. Co-occurring genomic alterations, tumor mutational burden (TMB) and PD-L1 IHC (22C3, TPS score) were analyzed by KRAS mt type. Results: Across the entire cohort, 4706 (27%) of samples harbored a KRAS mt (Table). The most common was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mt was 37.2% among adenocarcinoma and only 4.4% in squamous. High TMB, defined by > 10 mts/Mb, varied across the different KRAS mt types, most common in G13X (68.3%) and least common in G12D (43.2%). PD-L1 expression also varied. G12C was the most likely to be PD-L1 positive, with 65.5% TPS > 1%, and the most likely to be PD-L1 high, with 41.3% TPS > 50%. STK11 was mutated in 8.6% of KRAS wild type NSCLC but more frequently noted in every KRAS subtype, with the highest rate in G13X (36.2%) and the lowest in G12D(14.2%). TP53 mts were more frequent in KRAS wild type NSCLC (73.6%), with the highest rate among KRAS mutants at 55.4% (G12other) and the lowest at 36.8% (Q61X). NF1 was noted to be mutated in 21.4% of KRAS G13X cases, while all other KRAS mts had a lower frequency of NF1 mts than KRAS wild type (11.5%). Conclusions: KRAS mts are relatively common in lung adenocarcinoma and KRAS G12C is the most common variant. The different KRAS mts have different co-occurring mutations and a different genomic landscape. KRAS G12C was associated with the highest rate of PD-L1 expression. The clinical relevance of these differences in the context of therapeutic intervention warrants investigation. [Table: see text

Characterization of KRAS Mutation Subtypes in Non–small Cell Lung Cancer

KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS-mutated non–small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development. Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of KRAS mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by KRAS mutation type. Across the cohort, 4,706 (27.5%) samples harbored a KRAS mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across KRAS mutation subtypes. KRAS G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). STK11 was mutated in 8.6% of KRAS wild-type NSCLC but more frequent in KRAS-mutant NSCLC, with the highest rate in G13 (36.2%). TP53 mutations were more frequent in KRAS wild-type NSCLC (73.6%). KRAS mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation