1,042 research outputs found

    Super-Resolved Enhancement of a Single Image and Its Application in Cardiac MRI

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    Super-resolved image enhancement is of great importance in medical imaging. Conventional methods often require multiple low resolution (LR) images from different views of the same object or learning from large amount of training datasets to achieve success. However, in real clinical environments, these prerequisites are rarely fulfilled. In this paper, we present a self-learning based method to perform superresolution (SR) from a single LR input. The mappings between the given LR image and its downsampled versions are modeled using support vector regression on features extracted from sparse coded dictionaries, coupled with dual-tree complex wavelet transform based denoising. We demonstrate the efficacy of our method in application of cardiac MRI enhancement. Both quantitative and qualitative results show that our SR method is able to preserve fine textural details that can be corrupted by noise, and therefore can maintain crucial diagnostic information

    Structure and mechanism of human DNA polymerase η

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    The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

    Strong and Tunable Nonlinear Optomechanical Coupling in a Low-Loss System

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    A major goal in optomechanics is to observe and control quantum behavior in a system consisting of a mechanical resonator coupled to an optical cavity. Work towards this goal has focused on increasing the strength of the coupling between the mechanical and optical degrees of freedom; however, the form of this coupling is crucial in determining which phenomena can be observed in such a system. Here we demonstrate that avoided crossings in the spectrum of an optical cavity containing a flexible dielectric membrane allow us to realize several different forms of the optomechanical coupling. These include cavity detunings that are (to lowest order) linear, quadratic, or quartic in the membrane's displacement, and a cavity finesse that is linear in (or independent of) the membrane's displacement. All these couplings are realized in a single device with extremely low optical loss and can be tuned over a wide range in situ; in particular, we find that the quadratic coupling can be increased three orders of magnitude beyond previous devices. As a result of these advances, the device presented here should be capable of demonstrating the quantization of the membrane's mechanical energy.Comment: 12 pages, 4 figures, 1 tabl

    Factorization and resummation of s-channel single top quark production

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    In this paper we study the factorization and resummation of s-channel single top quark production in the Standard Model at both the Tevatron and the LHC. We show that the production cross section in the threshold limit can be factorized into a convolution of hard function, soft function and jet function via soft-collinear-effective-theory (SCET), and resummation can be performed using renormalization group equation in the momentum space resummation formalism. We find that in general, the resummation effects enhance the Next-to-Leading-Order (NLO) cross sections by about 33%-5% at both the Tevatron and the LHC, and significantly reduce the factorization scale dependence of the total cross section at the Tevatron, while at the LHC we find that the factorization scale dependence has not been improved, compared with the NLO results.Comment: 29 pages, 7 figures; version published in JHE

    Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies

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    The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R. These residues are predicted to undergo substantial movement during the transition of the receptor ion channel from the closed to the open state, predictions which are made based on structural homology models generated from the crystal structures of the zebrafish P2X4R. Our results provide evidence that among the six pairs of cysteine mutants, D48C/I133C and K81C/V304C formed disulphide bonds that impaired the channel gating to support the notion that such conformational changes, particularly those in the outer ends of the transmembrane domains, are critical for human P2X7R activation

    Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts

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    We outline the scientific motivation behind a search for gravitational waves associated with short gamma ray bursts detected by the InterPlanetary Network (IPN) during LIGO's fifth science run and Virgo's first science run. The IPN localisation of short gamma ray bursts is limited to extended error boxes of different shapes and sizes and a search on these error boxes poses a series of challenges for data analysis. We will discuss these challenges and outline the methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on Gravitational Waves, July 2011, Cardiff, U

    Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

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    Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

    A half-site multimeric enzyme achieves its cooperativity without conformational changes

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    Cooperativity is a feature many multimeric proteins use to control activity. Here we show that the bacterial heptose isomerase GmhA displays homotropic positive and negative cooperativity among its four protomers. Most similar proteins achieve this through conformational changes: GmhA instead employs a delicate network of hydrogen bonds, and couples pairs of active sites controlled by a unique water channel. This network apparently raises the Lewis acidity of the catalytic zinc, thus increasing the activity at one active site at the cost of preventing substrate from adopting a reactive conformation at the paired negatively cooperative site – a “half-site” behavior. Our study establishes the principle that multimeric enzymes can exploit this cooperativity without conformational changes to maximize their catalytic power and control. More broadly, this subtlety by which enzymes regulate functions could be used to explore new inhibitor design strategies

    Reactivity of Metal-Free and Metal-Associated Amyloid-?? with Glycosylated Polyphenols and Their Esterified Derivatives

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    Both amyloid-?? (A??) and transition metal ions are shown to be involved in the pathogenesis of Alzheimer???s disease (AD), though the importance of their interactions remains unclear. Multifunctional molecules, which can target metal-free and metal-bound A?? and modulate their reactivity (e.g., A?? aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free/-associated A??, and further control both metal-free and metal-induced A?? aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy, and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound A??. Of the polyphenols investigated, the natural product (Verbascoside) and its esterified derivative (VPP) regulate the aggregation and cytotoxicity of metal-free and/or metal-associated A?? to different extents. Our studies indicate Verbascoside represents a promising structure for further multifunctional tool development against both metal-free A?? and metal-A??.open0
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