NFPA Fluid Powered Vehicle Challenge 2023

This report includes the design process undergone by Team Shifty in designing a vehicle for the NFPA’s Fluid Powered Vehicle challenge. The report covers the background of the competition, research done by the team, engineering specifications for the design, preliminary and final designs, the manufacturing plan and process, project management details, and several recommendations for future teams participating in the challenge. The National Fluid Power Association, NFPA, is a trade association with the goal of connecting fluid power companies and advancing fluid power. With the goal of advancement in mind, NFPA hosts an annual Fluid Powered Vehicle Challenge (FPVC). Since before the NFPA took over this challenge, Cal Poly has produced a team to compete. Team Shifty completed research into past Cal Poly teams as well as other competing university teams to define the engineering specifications for the new vehicle and decide the design directions. The final design includes a new frame to address issues with the last teams frame, a new hydraulic circuit design and selection of new components to improve the circuits performance in the FPVC events and reduce losses, and the addition of gear shifting to the vehicle. With respect to hydraulics, a new manifold was sourced to accommodate the simplified fluid circuit, along with a larger motor to allow the vehicle to operate at higher torque. The prior team’s pneumatic system was completely replaced by a pneumatic front gear shifting system. The electronics implemented was the same system as the previous year, including an STM microcontroller, Nextion touch screen display, and Hydraforce valve operator with only two solenoid valves. Working together, these components allowed the rider to toggle between three unique drive modes, including: direct, regen, and sprint. To produce a functional vehicle, research and planning was put into manufacturing and assembly processes as detailed in the manufacturing plan. The final product failed to perform as proposed in Team Shifty’s Scope of Work, as the vehicle’s rear chain consistently fell off during operation at the competition. This resulted in the vehicle not placing during a few of the challenges, including the Sprint and Endurance races. The cause of this failure was a function of the frame flexing under dynamic loading due to insufficient torsional stiffness, as well as the rear chain being too small to handle the large output torque of the upsized rear motor

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

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