High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

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

ASIC implementation and optimization of 16 bit SDRAM memory controller

Last-level caches (LLC) often used to relay between the central processing unit (CPU) and the main memory. Most traditional processor used static-random-access-memory (SRAM) as the cache storage. Other technologies such as embedded dynamic-random-access-memory (eDRAM) and Synchronous Dynamic Random Access Memory (SDRAM) have also been implemented to store the caches information. SDRAM able to achieve a higher data transfer rates than asynchronous Dynamic Random Access Memory (DRAM). A memory controller is needed to manage the data flow. However, today issue's is the speed of fetching data from memories is unable to cope up the processors' speed since processors are getting faster day by day. Beside the speed limitation, a high-speed memory controller will also consume high dynamic power. Due to this fact, an optimized memory controller is needed to reduce the dynamic power used by the memory controller. This work proposed a reduction of dynamic power of the memory controller by reducing the switching activities. The focus of this work is to implement the design in Application Specific Integrated Circuit (ASIC) with switching power optimization of clock gating method. The clock gating cell is implemented in DC while optimized in ICC. It is found that the clock gating method able to reduce the percentage of switching power to 23% with average clock toggle rate saving of 41.6%. Besides, the voltage drop in the power network is also less than 10% which is 44.4mV or 2.22%. This work has proved that implementing of clock gating in the design is able to reduce the switching power and dynamic power without sacrificed the clock frequency

Multi-stage identification scheme for detecting damage in structures under ambient excitations

Structural damage identification methods are critical to the successful application of structural health monitoring (SHM) systems to civil engineering structures. The dynamic response of civil engineering structures is usually characterized by high nonlinearity and non-stationarity. Accordingly, an improved Hilbert-Huang transform (HHT) method which is adaptive, output-only and applicable to system identification of in-service structures under ambient excitations is developed in this study. Based on this method, a multi-stage damage detection scheme including the detection of damage occurrence, damage existence, damage location and the estimation of damage severity is developed. In this scheme, the improved HHT method is used to analyse the structural acceleration response, the obtained instantaneous frequency detects the instant of damage occurrence, the instantaneous phase is sensitive to minor damage and provides reliable damage indication, and the damage indicator developed based on statistical analysis of the Hilbert marginal spectrum detects damage locations. Finally, the response sampled at the detected damage location is continuously analysed to estimate the damage severity. Numerical and experimental studies of frame structures under ambient excitations are performed. The results demonstrate that this scheme accomplishes the above damage detection functions within one flow. It is robust, time efficient, simply implemented and applicable to the real-time SHM of in-service structures

In situ powder diffraction studies of electrode materials in rechargeable batteries

The ability to directly track the charge carrier in a battery as it inserts/extracts from an electrode during charge/discharge provides unparalleled insight for researchers into the working mechanism of the device. This crystallographic-electrochemical information can be used to design new materials or modify electrochemical conditions to improve battery performance characteristics, such as lifetime. Critical to collecting operando data used to obtain such information insitu while a battery functions are X-ray and neutron diffractometers with sufficient spatial and temporal resolution to capture complex and subtle structural changes. The number of operando battery experiments has dramatically increased in recent years, particularly those involving neutron powder diffraction. Herein, the importance of structure-property relationships to understanding battery function, why insitu experimentation is critical to this, and the types of experiments and electrochemical cells required to obtain such information are described. For each battery type, selected research that showcases the power of insitu and operando diffraction experiments to understand battery function is highlighted and future opportunities for such experiments are discussed. The intention is to encourage researchers to use insitu and operando techniques and to provide a concise overview of this area of research