A preliminary design study of a microparticle accelerator final report, 30 jan. - 13 apr. 1964

Design study for 2MV microparticle accelerato

Anomalous Ising freezing times

We measure the relaxation time of a square lattice Ising ferromagnet that is quenched to zero-temperature from supercritical initial conditions. We reveal an anomalous and seemingly overlooked timescale associated with the relaxation to ‘frozen’ two-stripe states. While close to a power law of the form ∼ L^ν , we argue this timescale actually grows as L^2 ln L, with L the linear dimension of the system. We uncover the mechanism behind this scaling form by using a synthetic initial condition that replicates the late time ordering of two-stripe states, and subsequently explain it heuristically

Empirical ways to identify novel Bedaquiline resistance mutations in AtpE.

Clinical resistance against Bedaquiline, the first new anti-tuberculosis compound with a novel mechanism of action in over 40 years, has already been detected in Mycobacterium tuberculosis. As a new drug, however, there is currently insufficient clinical data to facilitate reliable and timely identification of genomic determinants of resistance. Here we investigate the structural basis for M. tuberculosis associated bedaquiline resistance in the drug target, AtpE. Together with the 9 previously identified resistance-associated variants in AtpE, 54 non-resistance-associated mutations were identified through comparisons of bedaquiline susceptibility across 23 different mycobacterial species. Computational analysis of the structural and functional consequences of these variants revealed that resistance associated variants were mainly localized at the drug binding site, disrupting key interactions with bedaquiline leading to reduced binding affinity. This was used to train a supervised predictive algorithm, which accurately identified likely resistance mutations (93.3% accuracy). Application of this model to circulating variants present in the Asia-Pacific region suggests that current circulating variants are likely to be susceptible to bedaquiline. We have made this model freely available through a user-friendly web interface called SUSPECT-BDQ, StrUctural Susceptibility PrEdiCTion for bedaquiline (http://biosig.unimelb.edu.au/suspect_bdq/). This tool could be useful for the rapid characterization of novel clinical variants, to help guide the effective use of bedaquiline, and to minimize the spread of clinical resistance.M.K was funded by the Melbourne Research Scholarship. D.B.A was funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1), the Jack Brockhoff Foundation (JBF 4186, 2016), and a C. J. Martin Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1072476). The Vietnam genomic dataset was funded by a NHMRC Australia grant (APP1056689) to SJD and KEH. Supported in part by the Victorian Government's OIS Program

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses

Rapid Artefact Removal and H&E-Stained Tissue Segmentation

We present an innovative method for rapidly segmenting hematoxylin and eosin (H&E)-stained tissue in whole-slide images (WSIs) that eliminates a wide range of undesirable artefacts such as pen marks and scanning artefacts. Our method involves taking a single-channel representation of a lowmagnification RGB overview of the WSI in which the pixel values are bimodally distributed suchthat H&E-stained tissue is easily distinguished from both background and a wide variety of artefacts. We demonstrate our method on 30 WSIs prepared from a wide range of institutions and WSI digital scanners, each containing substantial artefacts, and compare it to segmentations provided by Otsu thresholding and Histolab tissue segmentation and pen filtering tools. We found that our methodsegmented the tissue and fully removed all artefacts in 29 out of 30 WSIs, whereas Otsu thresholding failed to remove any artefacts, and the Histolab pen filtering tools only partially removed the pen marks. The beauty of our approach lies in its simplicity: manipulating RGB colour space and using Otsu thresholding allows for the segmentation of H&E-stained tissue and the rapid removal ofartefacts without the need for machine learning or parameter tuning

Susceptibility of cat fleas (siphonaptera: Puclicidae) to fipronil and imidacloprid using adult and larval bioassays

© 2014 Entomological Society of America This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] monitoring of the susceptibility offleas to insecticides has typically been conducted by exposing adults on treated surfaces. Other methods such as topical applications of insecticides to adults and larval bioassays on treated rearing media have been developed. Unfortunately, baseline responses of susceptible strains of cat flea, Ctenocephalides felis (Bouchè), except for imidacloprid, have not been determined for all on-animal therapies and new classes of chemistry now being used. However, the relationship between adult and larval bioassays of fleas has not been previously investigated. The adult and larval bioassays of fipronil and imidacloprid were compared for both field-collected isolates and laboratory strains. Adult topical bioassays of fipronil and imidacloprid to laboratory strains and field-collected isolates demonstrated that LD50s of fipronil and imidacloprid ranged from 0.11 to 0.40 nanograms per flea and 0.02 to 0.18 nanograms per flea, respectively. Resistance ratios for fipronil and imidacloprid ranged from 0.11 to 2.21. Based on the larval bioassay published for imidacloprid, a larval bioassay was established for fipronil and reported in this article. The ranges of the LC50s of fipronil and imidacloprid in the larval rearing media were 0.07-0.16 and 0.11-0.21 ppm, respectively. Resistance ratios for adult and larval bioassays ranged from 0.11 to 2.2 and 0.58 to 1.75, respectively. Both adult and larval bioassays provided similar patterns for fipronil and imidacloprid. Although the adult bioassays permitted a more precise dosage applied, the larval bioassays allowed for testing isolates without the need to maintain on synthetic or natural hosts.Peer reviewedFinal Published versio

Fundamental Drivers of the Cost and Price of Operating Reserves

Operating reserves impose a cost on the electric power system by forcing system operators to keep partially loaded spinning generators available for responding to system contingencies variable demand. In many regions of the United States, thermal power plants provide a large fraction of the operating reserve requirement. Alternative sources of operating reserves, such as demand response and energy storage, may provide more efficient sources of these reserves. However, to estimate the potential value of these services, the cost of reserve services under various grid conditions must first be established. This analysis used a commercial grid simulation tool to evaluate the cost and price of several operating reserve services, including spinning contingency reserves and upward regulation reserves. These reserve products were evaluated in a utility system in the western United States, considering different system flexibilities, renewable energy penetration, and other sensitivities. The analysis demonstrates that the price of operating reserves depend highly on many assumptions regarding the operational flexibility of the generation fleet, including ramp rates and the fraction of fleet available to provide reserves

Structure guided prediction of Pyrazinamide resistance mutations in pncA

Abstract: Pyrazinamide plays an important role in tuberculosis treatment; however, its use is complicated by side-effects and challenges with reliable drug susceptibility testing. Resistance to pyrazinamide is largely driven by mutations in pyrazinamidase (pncA), responsible for drug activation, but genetic heterogeneity has hindered development of a molecular diagnostic test. We proposed to use information on how variants were likely to affect the 3D structure of pncA to identify variants likely to lead to pyrazinamide resistance. We curated 610 pncA mutations with high confidence experimental and clinical information on pyrazinamide susceptibility. The molecular consequences of each mutation on protein stability, conformation, and interactions were computationally assessed using our comprehensive suite of graph-based signature methods, mCSM. The molecular consequences of the variants were used to train a classifier with an accuracy of 80%. Our model was tested against internationally curated clinical datasets, achieving up to 85% accuracy. Screening of 600 Victorian clinical isolates identified a set of previously unreported variants, which our model had a 71% agreement with drug susceptibility testing. Here, we have shown the 3D structure of pncA can be used to accurately identify pyrazinamide resistance mutations. SUSPECT-PZA is freely available at: http://biosig.unimelb.edu.au/suspect_pza/