753 research outputs found

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    SMOG 2: A versatile software package for generating structure-based models

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    Molecular dynamics simulations with coarse-grained or simplified Hamiltonians have proven to be an effective means of capturing the functionally important long-time and large-length scale motions of proteins and RNAs. Originally developed in the context of protein folding, structure-based models (SBMs) have since been extended to probe a diverse range of biomolecular processes, spanning from protein and RNA folding to functional transitions in molecular machines. The hallmark feature of a structure-based model is that part, or all, of the potential energy function is defined by a known structure. Within this general class of models, there exist many possible variations in resolution and energetic composition. SMOG 2 is a downloadable software package that reads user-designated structural information and user-defined energy definitions, in order to produce the files necessary to use SBMs with high performance molecular dynamics packages: GROMACS and NAMD. SMOG 2 is bundled with XML-formatted template files that define commonly used SBMs, and it can process template files that are altered according to the needs of each user. This computational infrastructure also allows for experimental or bioinformatics-derived restraints or novel structural features to be included, e.g. novel ligands, prosthetic groups and post-translational/transcriptional modifications. The code and user guide can be downloaded at http://smog-server.org/smog2

    Superconductors with Magnetic Impurities: Instantons and Sub-gap States

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    When subject to a weak magnetic impurity potential, the order parameter and quasi-particle energy gap of a bulk singlet superconductor are suppressed. According to the conventional mean-field theory of Abrikosov and Gor'kov, the integrity of the energy gap is maintained up to a critical concentration of magnetic impurities. In this paper, a field theoretic approach is developed to critically analyze the validity of the mean field theory. Using the supersymmetry technique we find a spatially homogeneous saddle-point that reproduces the Abrikosov-Gor'kov theory, and identify instanton contributions to the density of states that render the quasi-particle energy gap soft at any non-zero magnetic impurity concentration. The sub-gap states are associated with supersymmetry broken field configurations of the action. An analysis of fluctuations around these configurations shows how the underlying supersymmetry of the action is restored by zero modes. An estimate of the density of states is given for all dimensionalities. To illustrate the universality of the present scheme we apply the same method to study `gap fluctuations' in a normal quantum dot coupled to a superconducting terminal. Using the same instanton approach, we recover the universal result recently proposed by Vavilov et al. Finally, we emphasize the universality of the present scheme for the description of gap fluctuations in d-dimensional superconducting/normal structures.Comment: 18 pages, 9 eps figure

    Near-Surface Interface Detection for Coal Mining Applications Using Bispectral Features and GPR

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    The use of ground penetrating radar (GPR) for detecting the presence of near-surface interfaces is a scenario of special interest to the underground coal mining industry. The problem is difficult to solve in practice because the radar echo from the near-surface interface is often dominated by unwanted components such as antenna crosstalk and ringing, ground-bounce effects, clutter, and severe attenuation. These nuisance components are also highly sensitive to subtle variations in ground conditions, rendering the application of standard signal pre-processing techniques such as background subtraction largely ineffective in the unsupervised case. As a solution to this detection problem, we develop a novel pattern recognition-based algorithm which utilizes a neural network to classify features derived from the bispectrum of 1D early time radar data. The binary classifier is used to decide between two key cases, namely whether an interface is within, for example, 5 cm of the surface or not. This go/no-go detection capability is highly valuable for underground coal mining operations, such as longwall mining, where the need to leave a remnant coal section is essential for geological stability. The classifier was trained and tested using real GPR data with ground truth measurements. The real data was acquired from a testbed with coal-clay, coal-shale and shale-clay interfaces, which represents a test mine site. We show that, unlike traditional second order correlation based methods such as matched filtering which can fail even in known conditions, the new method reliably allows the detection of interfaces using GPR to be applied in the near-surface region. In this work, we are not addressing the problem of depth estimation, rather confining ourselves to detecting an interface within a particular depth range

    The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma

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    Contains fulltext : 208930.pdf (publisher's version ) (Open Access)BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease

    Cutoff for the Ising model on the lattice

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    Introduced in 1963, Glauber dynamics is one of the most practiced and extensively studied methods for sampling the Ising model on lattices. It is well known that at high temperatures, the time it takes this chain to mix in L1L^1 on a system of size nn is O(logn)O(\log n). Whether in this regime there is cutoff, i.e. a sharp transition in the L1L^1-convergence to equilibrium, is a fundamental open problem: If so, as conjectured by Peres, it would imply that mixing occurs abruptly at (c+o(1))logn(c+o(1))\log n for some fixed c>0c>0, thus providing a rigorous stopping rule for this MCMC sampler. However, obtaining the precise asymptotics of the mixing and proving cutoff can be extremely challenging even for fairly simple Markov chains. Already for the one-dimensional Ising model, showing cutoff is a longstanding open problem. We settle the above by establishing cutoff and its location at the high temperature regime of the Ising model on the lattice with periodic boundary conditions. Our results hold for any dimension and at any temperature where there is strong spatial mixing: For Z2\Z^2 this carries all the way to the critical temperature. Specifically, for fixed d1d\geq 1, the continuous-time Glauber dynamics for the Ising model on (Z/nZ)d(\Z/n\Z)^d with periodic boundary conditions has cutoff at (d/2λ)logn(d/2\lambda_\infty)\log n, where λ\lambda_\infty is the spectral gap of the dynamics on the infinite-volume lattice. To our knowledge, this is the first time where cutoff is shown for a Markov chain where even understanding its stationary distribution is limited. The proof hinges on a new technique for translating L1L^1 to L2L^2 mixing which enables the application of log-Sobolev inequalities. The technique is general and carries to other monotone and anti-monotone spin-systems.Comment: 34 pages, 3 figure

    Failing boys and moral panics: perspectives on the underachievement debate

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    The paper re-examines the underachievement debate from the perspective of the ‘discourse of derision’ that surrounds much writing in this area. It considers the contradictions and inconsistencies which underpin much of the discourse – from a reinterpretation of examination scores, to the conflation of the concepts of ‘under’ and ‘low’ achievement and finally to the lack of consensus on a means of defining and measuring the term underachievement. In doing so, this paper suggests a more innovative approach for understanding, re-evaluating and perhaps rejecting the notion of underachievement

    Targeting the Ataxia Telangiectasia Mutated-null Phenotype in Chronic Lymphocytic Leukemia with Pro-oxidants

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    Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumours with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia
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