2,012 research outputs found

    Optically and electrically tunable graphene quantum dot–polyaniline composite films

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    Graphene quantum dot-polyaniline (PANI-GQD) composite films were synthesized by a chemical oxidation polymerization process. The optical properties of the PANI-GQD composite were studied by varying the mole concentration of PANI and the size of the GQDs. The Au/PANI-GQDs/ITO sandwich device was fabricated in order to investigate the transport properties of the composite. A stable hysteresis loop was observed in response to the applied voltage. By varying the PANI content and size of the GQDs, the area within the hysteresis loop and electrical conductance behavior of the device can be tuned in a controlled manner. Both the tunable luminescence and electrical hysteresis behavior are attributed to surface states of the GQDs. The PANI-GQD composite films are expected to find application in photonic devices.Department of Applied Physic

    A novel feature selection-based sequential ensemble learning method for class noise detection in high-dimensional data

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    © 2018, Springer Nature Switzerland AG. Most of the irrelevant or noise features in high-dimensional data present significant challenges to high-dimensional mislabeled instances detection methods based on feature selection. Traditional methods often perform the two dependent step: The first step, searching for the relevant subspace, and the second step, using the feature subspace which obtained in the previous step training model. However, Feature subspace that are not related to noise scores and influence detection performance. In this paper, we propose a novel sequential ensemble method SENF that aggregate the above two phases, our method learns the sequential ensembles to obtain refine feature subspace and improve detection accuracy by iterative sparse modeling with noise scores as the regression target attribute. Through extensive experiments on 8 real-world high-dimensional datasets from the UCI machine learning repository [3], we show that SENF performs significantly better or at least similar to the individual baselines as well as the existing state-of-the-art label noise detection method

    Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

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    We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido

    Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

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    In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity

    Keratoconus associated with choroidal neovascularization: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Keratoconus and choroidal neovascularization can occur as a result of dysfunction of the epithelium and its basement membrane.</p> <p>Case presentation</p> <p>A 17-year-old Asian man, who was diagnosed with myopic choroidal neovascularization in both eyes and who subsequently underwent intravitreal injection of ranibizumab (Lucentis<sup>®</sup>) five times over six months, presented with further vision decrease and pain in his right eye. Examination showed corneal steepening and stromal edema in the inferocentral cornea of his right eye, both of which were indicative of advanced keratoconus with acute hydrops. Corneal topography also showed features consistent with keratoconus in his left eye. Fluorescein angiography and optical coherence tomography revealed choroidal neovascularization-associated subretinal hemorrhages and lacquer cracks in both eyes.</p> <p>Conclusion</p> <p>Keratoconus and choroidal neovascularization, possibly resulting from dysfunction of the epithelium and its basement membrane, can occur together in the same individual. This would suggest a possible connection in pathogenesis between these two conditions.</p

    Anti-Arthritic Effects of Magnolol in Human Interleukin 1β-Stimulated Fibroblast-Like Synoviocytes and in a Rat Arthritis Model

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    Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5′-Diallyl-biphenyl-2,2′-diol), the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL)-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E2, and matrix metalloproteinases (MMPs) by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5–25 µg/mL). In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg) significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases

    Promoting influenza prevention for elderly people in Hong Kong using health action process approach: Study protocol

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    Background: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people's behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA). Methods: The target group is Hong Kong Chinese elderly people aged 65 or older who rarely or never adopt any preventive actions. This project will be conducted in three phases over 24 months. In phase 1, intervention program will be developed building on the HAPA theoretical framework which comprises both the initiation and maintenance of influenza prevention behaviors. In phase 2, intervention will be implemented and evaluated using a randomized controlled trial, including: (a) behavior initiation only, (b) behavior initiation + behavior maintenance, and (c) control group. Both the initiation and maintenance components will comprise weekly-delivered telephone-based individual intervention sessions in 3 months. In phase 3, outcome evaluation of behavioral and psychological variables and process evaluation will be conducted. The effectiveness of the intervention will be analyzed using a series of linear mixed models on each behavioral and psychological outcome variable. Structural equation modelling will be used to test the hypothesized theoretical sequence in the HAPA model. Discussion: The proposed project is expected to design theory-based intervention materials to promote the influenza prevention behaviors in Hong Kong elderly people and provide information on its effectiveness and the potential changing mechanism of behavior initiation and maintenance. Trial registration: This randomized controlled trial was funded by the Health and Medical Research Fund (HMRF), Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (Ref: 16151222) and was registered on 13/10/2017 at CCRB Clinical Trials Registry of the Chinese University of Hong Kong, a Partner Registry of a WHO Primary Registry (Ref: CUHK-CCRB00567)

    Prediction of peptide and protein propensity for amyloid formation

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    Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation
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