Quick actuating closure and handling system

A quick activating closure and handling system, which utilizes conical sections for locking, was developed to allow quick access to the combustor internal components of the 8 ft High Temperature Tunnel. These critical components include the existing methane spraybar, a transpiration cooled nozzle and the new liquid oxygen (LOX) injection system housed within the combustor. A substantial cost savings will be realized once the mechanism is installed since it will substantially reduce the access time and increase the time available for conducting wind tunnel tests. A need exists for more frequent inspections when the wind tunnel operates at the more severe conditions generated by using LOX in the combustor. A loads analysis and a structural (finite element) analysis were conducted to verify that the new closure system is compatible with the existing pressure shell. In addition, strain gages were placed on the pressure vessel to verify how the pressure shell reacts to transient pressure loads. A scale model of the new closure system was built to verify the operation of the conical sections in the locking mechanisms

Multimessenger parameter inference of gravitational-wave and electromagnetic observations of white dwarf binaries

The upcoming Laser Interferometer Space Antenna (LISA) will detect a large gravitational-wave foreground of Galactic white dwarf binaries. These sources are exceptional for their probable detection at electromagnetic wavelengths, some long before LISA flies. Studies in both gravitational and electromagnetic waves will yield strong constraints on system parameters not achievable through measurements of one messenger alone. In this work, we present a Bayesian inference pipeline and simulation suite in which we study potential constraints on binaries in a variety of configurations. We show how using LISA detections and parameter estimation can significantly improve constraints on system parameters when used as a prior for the electromagnetic analyses. We also provide rules of thumb for how current measurements will benefit from LISA measurements in the future.Comment: 8 pages, 5 figures, accepted to MNRA

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements

Worker/wrapper/makes it/faster

Much research in program optimization has focused on formal approaches to correctness: proving that the meaning of programs is preserved by the optimisation. Paradoxically, there has been comparatively little work on formal approaches to efficiency: proving that the performance of optimized programs is actually improved. This paper addresses this problem for a general-purpose optimization technique, the worker/wrapper transformation. In particular, we use the call-by-need variant of improvement theory to establish conditions under which the worker/wrapper transformation is formally guaranteed to preserve or improve the time performance of programs in lazy languages such as Haskell

Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis

Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity—a worldwide public health concern—is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas–Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner

Anglican clergy husbands securing middle-class gendered privilege through religion

Traditionally, clergy wives have been obliged to assist the Church in an unpaid capacity; such work has been feminised, associated with the assumed competencies of women (Denton 1962; Finch 1980, 1983; Murphy-Geiss 2011). Clergy husbands are a relatively recent phenomenon in the Church of England, emerging when women started to be ordained as deacons in 1987 and priests in 1994. Based on interviews with men whose wives were ordained as priests in the Church of England, this article will explore the dynamics of class and gender privilege. Most clergy husbands were middle class, defined through educational, occupational and cultural markers (Bourdieu 1984). The narratives highlighted how gender and class privilege was maintained and extended through the clergy spouse role. The interweaving dynamics of class and gender privilege secured preferential outcomes for participants; outcomes that were less evidenced in relation to working-class spouses. Using Bourdieu’s (1984) concepts of habitus, field and capital and Verter’s (2003) conceptualisation of spiritual capital, this article will highlight the complex ways in which gender and class advantage is perpetuated and sustained, using the Anglican parish as the analytical context, thereby emphasising the role religion plays in consolidating privilege

Early Inception of the Laramide Orogeny in Southwestern Montana and Northern Wyoming: Implications for Models of Flat‐Slab Subduction

Timing and distribution of magmatism, deformation, exhumation, and basin development have been used to reconstruct the history of Laramide flat-slab subduction under North America during Late Cretaceous-early Cenozoic time. Existing geodynamic models, however, ignore a large (40,000-km(2)) sector of the Laramide foreland in southwestern Montana. The Montana Laramide ranges consist of Archean basement arches (fault-propagation folds) that were elevated by thrust and reverse faults. We present new thermochronological and geochronological data from six Laramide ranges in southwestern Montana (the Beartooth, Gravelly, Ruby and Madison Ranges, and the Tobacco Root and Highland Mountains) that show significant cooling and exhumation during the Early to mid-Cretaceous, much earlier than the record of Laramide exhumation in Wyoming. These data suggest that Laramide-style deformation-driven exhumation slightly predates the eastward sweep of magmatism in western Montana, consistent with geodynamic models involving initial strain propagation into North American cratonic rocks due to stresses associated with a northeastward expanding region of flat-slab subduction. Our results also indicate various degrees of Cenozoic heating and cooling possibly associated with westward rollback of the subducting Farallon slab, followed by Basin-and-Range extension. Plain Language Summary The Laramide region in the western U.S. is characterized by some of the highest topography in North America including the Wind River Range in WY and the Beartooth Range of WY and Montana. These ranges have fed detritus to surrounding basins for millions of years and contributed to modern ecosystems. These high topographic features and basins have significantly impacted paleoenvironmental conditions over geological time. The formation of these high-relief ranges has been linked to deep Earth, geodynamic, processes involving subduction of a flat slab under the North American Plate. Models of flat-slab subduction rely on the timing and pattern of deformation and exhumation of Laramide ranges, which remains poorly understood. Our study provides new data on the timing of deformation and exhumation of Laramide ranges in SW Montana and northern WY capable of testing current models of flat-slab subduction.NSF-Tectonics [EAR-1524151]6 month embargo; published online: 9 January 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Everything old is new again: Quoted Domain Specific Languages

We describe a new approach to domain specific languages (DSLs), called Quoted DSLs (QDSLs), that resurrects two old ideas: quotation, from McCarthy's Lisp of 1960, and the subformula property, from Gentzen's natural deduction of 1935. Quoted terms allow the DSL to share the syntax and type system of the host language. Normalising quoted terms ensures the subformula property, which guarantees that one can use higher-order types in the source while guaranteeing first-order types in the target, and enables using types to guide fusion. We test our ideas by re-implementing Feldspar, which was originally implemented as an Embedded DSL (EDSL), as a QDSL; and we compare the QDSL and EDSL variants