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  • Articles  (275)
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  • 1
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    On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-07
    Description: Type II topoisomerases (Top2s) alter DNA topology via the formation of an enzyme–DNA adduct termed cleavage complex, which harbors a transient double-strand break in one DNA to allow the passage of another. Agents targeting human Top2s are clinically active anticancer drugs whose trapping of Top2-mediated DNA breakage effectively induces genome fragmentation and cell death. To understand the structural basis of this drug action, we previously determined the structure of human Top2 β-isoform forming a cleavage complex with the drug etoposide and DNA, and described the insertion of drug into DNA cleavage site and drug-induced decoupling of catalytic groups. By developing a post-crystallization drug replacement procedure that simplifies structural characterization of drug-stabilized cleavage complexes, we have extended the analysis toward other structurally distinct drugs, m -AMSA and mitoxantrone. Besides the expected drug intercalation, a switch in ribose puckering in the 3'-nucleotide of the cleavage site was robustly observed in the new structures, representing a new mechanism for trapping the Top2 cleavage complex. Analysis of drug-binding modes and the conformational landscapes of the drug-binding pockets provide rationalization of the drugs’ structural-activity relationships and explain why Top2 mutants exhibit differential effects toward each drug. Drug design guidelines were proposed to facilitate the development of isoform-specific Top2-targeting anticancer agents.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke (2013)
    Springer Nature
    Details
    Publication Date: 2013-09-06
    Description: Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke Cell Death and Disease 4, e790 (September 2013). doi:10.1038/cddis.2013.326 Authors: D Yang-Wei Fann, S-Y Lee, S Manzanero, S-C Tang, M Gelderblom, P Chunduri, C Bernreuther, M Glatzel, Y-L Cheng, J Thundyil, A Widiapradja, K-Z Lok, S L Foo, Y-C Wang, Y-I Li, G R Drummond, M Basta, T Magnus, D-G Jo, M P Mattson, C G Sobey & T V Arumugam
    Keywords: IVIgischemic strokeinflammasomecell deathcaspase
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 3
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    Permian fusuline biostratigraphy (2017)
    Geological Society (of London)
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    Publication Date: 2017-09-30
    Description: A review of Permian fusuline biostratigraphy is made in this paper in order to improve the correlation of Permian strata globally. Permian fusuline biostratigraphy in the Tethyan and Panthalassan regions can be correlated roughly because the fusulines had good faunal communications between these two regions. However, fusuline faunas from the North American Craton region were devoid of almost all neoschwagerinids and dominated exclusively by schwagerinids during the Guadalupian (Middle Permian) because of the blockage caused by the vast Pangaea supercontinent. This renders the correlation of Middle Permian biostratigraphy and chronostratigraphy between the Tethyan region and North American region challenging. Significant evolutionary key points in fusulines include the first occurrence of Pseudoschwagerina or Sphaeroschwagerina during the earliest Permian, first occurrence of Pamirina and Misellina during the Yakhtashian and Bolorian, and the extinction of all schwagerinids and neoschwagerinids by the end of the Midian.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
    Published by Geological Society (of London)
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  • 4
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    A New Type Hi-Speed BLDC Control System Base on Indirect Current Control Strategy (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-05-10
    Description: High speed BLDC has the characteristic as larger air gap smaller armature inductance, traditional PWM modulation will produce a great number of high frequency current harmonics which led problem like large torque ripple and serious motor heat. In the meantime traditional PWM modulation use the diode rectifier which cause harmonic pollution in electric power net. To solve the problem above, proposes a new motor controller topology. Using the IGBT device to replace the diode on frequency converter rectifier side, apply the power factor correction technology, reduce the pollution on the grid. Using busbar current modulation on the inverter, driving bridge-arm use 3-phase 6-state open as driving Mode, realize the control on a 10000r/min,10kw BLDC. The results of Simulation on matlab show the topological structure as proposed can effectively improve the network side power factor and reduce the motor armature winding harmonic and motor torque ripple.
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 5
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    VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies (2013)
    Oxford University Press
    Details
    Publication Date: 2013-06-23
    Description: With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs. With improved understanding of the mechanisms of complex diseases and drug actions through network analysis, novel drug methods (e.g., drug repositioning, multi-target drug and combination therapy) can be designed. More specifically, the new update includes (i) integrated search and navigation of disease and drug hierarchies; (ii) integrated disease–gene, therapy–drug and drug–target association to aid the network construction and filtering; (iii) annotation of genes/drugs using disease/therapy information; (iv) prediction of associated diseases/therapies for a given set of genes/drugs using enrichment analysis; (v) network transformation to support construction of versatile network of drugs, genes, diseases and therapies; (vi) enhanced user interface using docking windows to allow easy customization of node and edge properties with build-in legend node to distinguish different node type. VisANT is freely available at: http://visant.bu.edu .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5β1-integrin (2013)
    Springer Nature
    Details
    Publication Date: 2013-06-07
    Description: Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5β1-integrin Cell Death and Disease 4, e651 (June 2013). doi:10.1038/cddis.2013.177 Authors: Y-C Wang, H-C Juan, Y-H Wong, W-C Kuo, Y-L Lu, S-F Lin, C-J Lu & M-J Fann
    Keywords: Radilbranchial archesbone formationintegrin
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 7
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    Influence of blade angle distribution along leading edge on cavitation performance of a centrifugal pump (2015)
    Institute of Physics (IOP)
    Details
    Publication Date: 2015-01-16
    Description: The influence of blade angle distribution along leading edge on cavitation performance of centrifugal pumps is analysed in the present paper. Three sets of blade angle distribution along leading edge for three blade inlet angles are chosen to design nine centrifugal pump impellers. The RNG k- ##IMG## [http://ej.iop.org/icons/Entities/epsilon.gif] {epsilon} turbulence model and the Zwart-Gerber-Belamri cavitation model are employed to simulate the cavitation flows in centrifugal pumps with different impellers and the same volute. The numerical results are compared with the experimental data, and the comparison proves that the numerical simulation can accurately predict the cavitation performance of centrifugal pumps. On the basis of the numerical simulations, the pump head variations with pump inlet pressure, and the flow details in centrifugal pump are revealed to demonstrate the influence of blade an...
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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  • 8
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    A model for 3:2 HFQPO pairs in black hole binaries based on cosmic battery (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-28
    Description: A model for 3:2 high-frequency quasi-periodic oscillations (HFQPOs) with 3:2 pairs observed in four black hole X-ray binaries (BHXBs) is proposed by invoking the epicyclic resonances with the magnetic connection (MC) between a spinning black hole (BH) with a relativistic accretion disc. It turns out that the MC can be worked out due to Poynting–Robertson cosmic battery, and the 3:2 HFQPO pairs associated with the steep power-law states can be fitted in this model. Furthermore, the severe damping problem in the epicyclic resonance model can be overcome by transferring energy from the BH to the inner disc via the MC process for emitting X-rays with sufficient amplitude and coherence to produce the HFQPOs. In addition, we discuss the important role of the magnetic field in state transition of BHXBs.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Solution structure and tandem DNA recognition of the C-terminal effector domain of PmrA from Klebsiella pneumoniae (2014)
    Oxford University Press
    Details
    Publication Date: 2014-04-03
    Description: Klebsiella pneumoniae PmrA is a polymyxin-resistance-associated response regulator. The C-terminal effector/DNA-binding domain of PmrA (PmrA C ) recognizes tandem imperfect repeat sequences on the promoters of genes to induce antimicrobial peptide resistance after phosphorylation and dimerization of its N-terminal receiver domain (PmrA N ). However, structural information concerning how phosphorylation of the response regulator enhances DNA recognition remains elusive. To gain insights, we determined the nuclear magnetic resonance solution structure of PmrA C and characterized the interactions between PmrA C or BeF 3 – -activated full-length PmrA (PmrA F ) and two DNA sequences from the pbgP promoter of K. pneumoniae . We showed that PmrA C binds to the PmrA box, which was verified to contain two half-sites, 5'-CTTAAT-3' and 5'-CCTAAG-3', in a head-to-tail fashion with much stronger affinity to the first than the second site without cooperativity. The structural basis for the PmrA C –DNA complex was investigated using HADDOCK docking and confirmed by paramagnetic relaxation enhancement. Unlike PmrA C , PmrA F recognizes the two sites simultaneously and specifically. In the PmrA F –DNA complex, PmrA N may maintain an activated homodimeric conformation analogous to that in the free form and the interactions between two PmrA C molecules aid in bending and binding of the DNA duplex for transcription activation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    A bio-inspired computing model for ovarian carcinoma classification and oncogene detection (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-03
    Description: Motivation: Ovarian cancer is the fifth leading cause of cancer deaths in women in the western world for 2013. In ovarian cancer, benign tumors turn malignant, but the point of transition is difficult to predict and diagnose. The 5-year survival rate of all types of ovarian cancer is 44%, but this can be improved to 92% if the cancer is found and treated before it spreads beyond the ovary. However, only 15% of all ovarian cancers are found at this early stage. Therefore, the ability to automatically identify and diagnose ovarian cancer precisely and efficiently as the tissue changes from benign to invasive is important for clinical treatment and for increasing the cure rate. This study proposes a new ovarian carcinoma classification model using two algorithms: a novel discretization of food sources for an artificial bee colony (DfABC), and a support vector machine (SVM). For the first time in the literature, oncogene detection using this method is also investigated. Results: A novel bio-inspired computing model and hybrid algorithms combining DfABC and SVM was applied to ovarian carcinoma and oncogene classification. This study used the human ovarian cDNA expression database to collect 41 patient samples and 9600 genes in each pathological stage. Feature selection methods were used to detect and extract 15 notable oncogenes. We then used the DfABC-SVM model to examine these 15 oncogenes, dividing them into eight different classifications according to their gene expressions of various pathological stages. The average accuracyof the eight classification experiments was 94.76%. This research also found some oncogenes that had not been discovered or indicated in previous scientific studies. The main contribution of this research is the proof that these newly discovered oncogenes are highly related to ovarian or other cancers. Availability and implementation: http://mht.mis.nchu.edu.tw/moodle/course/view.php?id=7 Contact: mychen@nutc.edu.tw
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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