611 research outputs found

    Theology, News and Notes - Vol. 22, No. 02

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    Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1054/thumbnail.jp

    Super-Hubbard models and applications

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    We construct XX- and Hubbard- like models based on unitary superalgebras gl(N|M) generalising Shastry's and Maassarani's approach of the algebraic case. We introduce the R-matrix of the gl(N|M) XX model and that of the Hubbard model defined by coupling two independent XX models. In both cases, we show that the R-matrices satisfy the Yang--Baxter equation, we derive the corresponding local Hamiltonian in the transfer matrix formalism and we determine the symmetry of the Hamiltonian. Explicit examples are worked out. In the cases of the gl(1|2) and gl(2|2) Hubbard models, a perturbative calculation at two loops a la Klein and Seitz is performed.Comment: 26 page

    Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures

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    Fragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community

    The effect of antibiotic selection on collateral effects and evolvability of uropathogenic Escherichia coli

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    Trimethoprim is recommended as a first-line treatment of urinary tract infections (UTIs) in the UK. In 2018, 31.4% of Escherichia coli isolated from UTIs in England were trimethoprim-resistant, leading to overreliance on other first and second-line antibiotics. Here, we assessed whether, in principle, prior selection with trimethoprim results in collateral effects to other antibiotics recommended for the treatment of UTIs. As collateral effects, we considered changes in susceptibility, mutation-selection window and population establishment probability. We selected 10 trimethoprim-resistant derivatives from three clinical isolates of uropathogenic Escherichia coli. We found that mutations conferring trimethoprim resistance did not have any collateral effects on fosfomycin. In contrast, resistance to trimethoprim resulted in decreased susceptibility (collateral resistance) to nitrofurantoin, below the clinical breakpoint and narrowed the mutation-selection window, thereby reducing the maximum concentration for selection of nitrofurantoin resistance mutations. Our analyses demonstrate that multiple collateral responses should be accounted for when predicting and optimising antibiotic use, limiting future antimicrobial resistance emergence

    Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

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    A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.United States. Department of Energy (Award DE-FC02-99ER54512)United States. Department of Energy (Grant DESC0014264

    Automaticity in sequence-space synaesthesia: a critical appraisal of the evidence

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    For many people, thinking about certain types of common sequence - for example calendar units or numerals - elicits a vivid experience that the sequence members occupy spatial locations which are in turn part of a larger spatial pattern of sequence members. Recent research on these visuospatial experiences has usually considered them to be a variety of synaesthesia, and many studies have argued that this sequence-space synaesthesia is an automatic process, consistent with a traditional view that automaticity is a key property of synaesthesia. In this review we present a critical discussion of data from the three main paradigms that have been used to argue for automaticity in sequence-space synaesthesia, namely SNARC-like effects (Spatial-Numerical-Association-of-Response-Codes), spatial cueing, and perceptual incongruity effects. We suggest that previous studies have been too imprecise in specifying which type of automaticity is implicated. Moreover, mirroring previous challenges to automaticity in other types of synaesthesia, we conclude that existing data are at best ambiguous regarding the automaticity of sequence-space synaesthesia, and may even be more consistent with the effects of controlled (i.e., non-automatic) processes. This lack of strong evidence for automaticity reduces the temptation to seek explanations of sequence-space synaesthesia in terms of processes mediated by qualitatively abnormal brain organization or mechanisms. Instead, more parsimonious explanations in terms of extensively rehearsed associations, established for example via normal processes of visuospatial imagery, are convergent with arguments that synaesthetic phenomena are on a continuum with normal cognition. (c) 2012 Elsevier Ltd. All rights reserved

    Metamorphosis of plasma turbulence-shear flow dynamics through a transcritical bifurcation

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    The structural properties of an economical model for a confined plasma turbulence governor are investigated through bifurcation and stability analyses. A close relationship is demonstrated between the underlying bifurcation framework of the model and typical behavior associated with low- to high-confinement transitions such as shear flow stabilization of turbulence and oscillatory collective action. In particular, the analysis evinces two types of discontinuous transition that are qualitatively distinct. One involves classical hysteresis, governed by viscous dissipation. The other is intrinsically oscillatory and non-hysteretic, and thus provides a model for the so-called dithering transitions that are frequently observed. This metamorphosis, or transformation, of the system dynamics is an important late side-effect of symmetry-breaking, which manifests as an unusual non-symmetric transcritical bifurcation induced by a significant shear flow drive.Comment: 17 pages, revtex text, 9 figures comprised of 16 postscript files. Submitted to Phys. Rev.

    BCS to Bose Crossover in Anisotropic Superconductors

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    In this work we use functional integral techniques to examine the nearest neighbour attractive Hubbard model on a quasi-2D lattice. It is a simple phenomenological model for the high-Tc cuprates that allows both extended (non-local) s- and d-wave singlet superconductivity as well as mixed symmetry states. The Hartree-Gor'kov mean field theory of the model has a finite temperature phase diagram which shows a transition from pure s-wave to pure d-wave superconductivity, via a mixed symmetry s+id state, as a function of doping. Including Gaussian fluctuations we examine the crossover from weak-coupling BCS superconductivity to the strong-coupling Bose-Einstein condensation of composite s- or d-wave bosons and comment on the origin and symmetry of the pseudogap.Comment: 20 pages inc. 13 figure

    Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM

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    The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC‐ISMRM) held a workshop entitled “Steps on the path to clinical translation” in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round‐table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community
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