Abstract: The ATLAS Google Project was established as part of an ongoing evaluation of the use of commercial clouds by the ATLAS Collaboration, in anticipation of the potential future adoption of such resources by WLCG grid sites to fulfil or complement their computing pledges. Seamless integration of Google cloud resources into the worldwide ATLAS distributed computing infrastructure was achieved at large scale and for an extended period of time, and hence cloud resources are shown to be an effective mechanism to provide additional, flexible computing capacity to ATLAS. For the first time a total cost of ownership analysis has been performed, to identify the dominant cost drivers and explore effective mechanisms for cost control. Network usage significantly impacts the costs of certain ATLAS workflows, underscoring the importance of implementing such mechanisms. Resource bursting has been successfully demonstrated, whilst exposing the true cost of this type of activity. A follow-up to the project is underway to investigate methods for improving the integration of cloud resources in data-intensive distributed computing environments and reducing costs related to network connectivity, which represents the primary expense when extensively utilising cloud resources.
The author witnessed the Chilean coup d'etat in 1973. Years later he finds José Emilio Pacheco's, the Mexican bard, report on the event.
Despite substantial reductions in the cost of sequencing over the last decade, genetic panels remain relevant due to their cost-effectiveness and flexibility across a variety of sample types. In particular, single nucleotide polymorphism (SNP) panels are increasingly favoured for conservation applications. SNP panels are often used because of their adaptability, effectiveness with low-quality samples, and cost-efficiency for population monitoring and forensics. However, the selection of diagnostic SNPs for population assignment and individual identification can be challenging. The consequences of poor SNP selection are under-powered panels, inaccurate results, and monetary loss. Here, we develop a novel and user-friendly SNP selection pipeline (mPCRselect) that can be used to select SNPs for population assignment and/or individual identification. mPCRselect allows any researcher, who has sufficient SNP-level data, to design a successful and cost-effective SNP panel for a diploid species of conservation concern.
With the low incidence of mutations in pediatric cancers, alternate genomic approaches are needed to identify therapeutic targets. Our study, the Comparative Analysis of RNA Expression to Improve Pediatric and Young Adult Cancer Treatment, was conducted by the UC Santa Cruz Treehouse Childhood Cancer Initiative and Stanford University School of Medicine. RNA sequencing data from 33 children and young adults with a relapsed, refractory or rare cancer underwent CARE analysis to reveal activated cancer driver pathways and nominate treatments. We compare our pipeline to other gene expression outlier detection approaches and discuss challenges for clinical implementation. Of our 33 patients, 31 (94%) had findings of potential clinical significance. Findings were implemented in 5 patients, 3 of which had defined clinical benefit. We demonstrate that comparator cohort composition determines which outliers are detected. This study highlights the clinical utility and challenges of implementing comparative RNA sequencing analysis in the clinic.
Great Aleutian underthrusting earthquakes produced destructive tsunamis impacting Hawaii in 1946 and 1957. Prior modeling of the 1957 tsunami deposit and runup records on eastern Aleutian and Hawaiian Islands jointly with tide-gauge observations across the Pacific Ocean constrained a rupture model with shallow slip up to 26 m along 600 km of the plate boundary. Here we implement this modeling approach to older deposits and show alternating deep and shallow megathrust slip up to 26, 32, and 22 m for great earthquakes along the same segment in the 18th, 15th, and 14th centuries. All three modeled prehistoric Aleutian earthquakes produce tsunami inundation in Hawaii with the most severe, 14th century event having impacts exceeding the 1957 event. The along-dip variability of these four ruptures spanning seven centuries provides insights on earthquake cycles for engineering design and hazard assessment. The 15th century and 1957 rupture models provide evidence for recurrence of tsunami earthquakes, which can produce disproportionately large tsunamis for a given moment magnitude due to reduced rigidity in the shallow megathrust. The 14th and 18th century events likely ruptured deeper regions that did not slip in 1957, suggesting potential for corresponding deeper failure in the next great eastern Aleutian earthquake.
PREMISE: Floral pigments such as anthocyanins are well known to influence pollinator attraction, yet they also confer tolerance to abiotic stressors such as harsh soils, extreme temperatures, low precipitation, and UV radiation. In such cases, environmental variation in abiotic stressors over space or time could lead to the maintenance of flower color variation within species. Under this scenario, flower color in natural populations should covary with environmental stressors. METHODS: Using a comparative approach, we tested whether abiotic variables predict flower color in Leptosiphon parviflorus, a species with pink and white flower color morphs. We conducted in-depth field studies to assess morph frequency, soil chemistry, and climate. We then employed community scientist-powered iNaturalist observations to examine patterns across even larger spatial scales. RESULTS: Across 21 field sites, L. parviflorus had a higher frequency of pink morphs in sites with serpentine soil, higher average annual temperatures, and higher average climatic water deficit (a proxy for drought stress). iNaturalist observations supported this finding-the probability of flowers being pink is greater in locations with serpentine-derived soil, especially when the local average UV radiation and climatic water deficit are higher. CONCLUSIONS: Spatial variation in abiotic stressors may contribute to the maintenance of flower color variation across the geographic range of L. parviflorus. Future studies will examine mechanisms by which flower color affects stress tolerance and will assess whether fitness trade-offs in contrasting habitats across the range are associated with flower color.
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.
