25 research outputs found

    Semi-supervised Domain Adaptation in Graph Transfer Learning

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    As a specific case of graph transfer learning, unsupervised domain adaptation on graphs aims for knowledge transfer from label-rich source graphs to unlabeled target graphs. However, graphs with topology and attributes usually have considerable cross-domain disparity and there are numerous real-world scenarios where merely a subset of nodes are labeled in the source graph. This imposes critical challenges on graph transfer learning due to serious domain shifts and label scarcity. To address these challenges, we propose a method named Semi-supervised Graph Domain Adaptation (SGDA). To deal with the domain shift, we add adaptive shift parameters to each of the source nodes, which are trained in an adversarial manner to align the cross-domain distributions of node embedding, thus the node classifier trained on labeled source nodes can be transferred to the target nodes. Moreover, to address the label scarcity, we propose pseudo-labeling on unlabeled nodes, which improves classification on the target graph via measuring the posterior influence of nodes based on their relative position to the class centroids. Finally, extensive experiments on a range of publicly accessible datasets validate the effectiveness of our proposed SGDA in different experimental settings

    Biomimetic total synthesis of (−)-galanthamine via intramolecular anodic aryl–phenol coupling

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    (−)-Galanthamine as a drug for the treatment of Alzheimer's disease has attracted synthetic chemists for decades. However, previous total synthetic and biomimetic approaches often use stoichiometric oxidants (metal oxidants or hypervalent iodine) to prepare the target product. Anodic oxidative coupling offers a sustainable alternative method which is, for the first time, successfully applied to the total synthesis of (−)-galanthamine. We report a new asymmetric total synthesis of (−)-galanthamine by using an anodic aryl–phenol coupling as the key synthetic step

    Vitamin E stabilizes iron and mitochondrial metabolism in pulmonary fibrosis

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    Introduction: Pulmonary fibrosis (PF) is a fatal chronic lung disease that causes structural damage and decreased lung function and has a poor prognosis. Currently, there is no medicine that can truly cure PF. Vitamin E (VE) is a group of natural antioxidants with anticancer and antimutagenic properties. There have been a few reports about the attenuation of PF by VE in experimental animals, but the molecular mechanisms are not fully understood.Methods: Bleomycin-induced PF (BLM-PF) mouse model, and cultured mouse primary lung fibroblasts and MLE 12 cells were utilized. Pathological examination of lung sections, immunoblotting, immunofluorescent staining, and real-time PCR were conducted in this study.Results: We confirmed that VE significantly delayed the progression of BLM-PF and increased the survival rates of experimental mice with PF. VE suppressed the pathological activation and fibrotic differentiation of lung fibroblasts and epithelial-mesenchymal transition and alleviated the inflammatory response in BLM-induced fibrotic lungs and pulmonary epithelial cells in vitro. Importantly, VE reduced BLM-induced ferritin expression in fibrotic lungs, whereas VE did not exhibit iron chelation properties in fibroblasts or epithelial cells in vitro. Furthermore, VE protected against mitochondrial dysmorphology and normalized mitochondrial protein expression in BLM-PF lungs. Consistently, VE suppressed apoptosis in BLM-PF lungs and pulmonary epithelial cells in vitro.Discussion: Collectively, VE markedly inhibited BLM-induced PF through a complex mechanism, including improving iron metabolism and mitochondrial structure and function, mitigating inflammation, and decreasing the fibrotic functions of fibroblasts and epithelial cells. Therefore, VE presents a highly potential therapeutic against PF due to its multiple protective effects with few side effects

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4‑Epi-Brefeldin A from D‑Glucose: Use of the Padwa Anionic Allenylsulfone [3+2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

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    A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3 + 2]-cycloadditive elimination. Cycloadduct <b>13</b> was initially elaborated into iodide <b>27</b>, which, following treatment with Zn, gave aldehyde <b>28</b> whose C(9) stereocenter was epimerized. Further elaboration into enoate <b>38</b> and Julia–Kocienski olefination with <b>5</b> subsequently afforded <b>39</b>, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the <i>seco</i>-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection

    Carreira Alkynylations with Paraformaldehyde. A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-SensitiveTerminal Acetylenes via Alkynylzinc Triflates

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    A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves <i>stoichiometric</i> Carreira alkynylation with solid paraformaldehyde (HO­[CH<sub>2</sub>O]<sub><i>n</i></sub>H) in PhMe at 60 °C. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metalation. While <i>N</i>-methylephedrine (NME) is generally the best Zn­(OTf)<sub>2</sub>-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement

    Oridonin Inhibits <i>Mycobacterium marinum</i> Infection-Induced Oxidative Stress In Vitro and In Vivo

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    Prior to the COVID-19 pandemic, tuberculosis (TB) was the leading cause of death globally attributable to a single infectious agent, ranking higher than HIV/AIDS. Consequently, TB remains an urgent public health crisis worldwide. Oridonin (7a,20-Epoxy-1a,6b,7,14-tetrahydroxy-Kaur-16-en-15-one Isodonol, C20H28O6, Ori), derived from the Rabdosia Rrubescens plant, is a natural compound that exhibits antioxidant, anti-inflammatory, and antibacterial properties. Our objective was to investigate whether Ori’s antioxidant and antibacterial effects could be effective against the infection Mycobacterium marinum (Mm)-infected cells and zebrafish. We observed that Ori treatment significantly impeded Mm infection in lung epithelial cells, while also suppressing inflammatory response and oxidative stress in Mm-infected macrophages. Further investigation revealed that Ori supplementation inhibited the proliferation of Mm in zebrafish, as well as reducing oxidative stress levels in infected zebrafish. Additionally, Ori promoted the expression of NRF2/HO-1/NQO-1 and activated the AKT/AMPK-α1/GSK-3β signaling pathway, which are both associated with anti-inflammatory and antioxidant effects. In summary, our results demonstrate that Ori exerts inhibitory effects on Mm infection and proliferation in cells and zebrafish, respectively. Additionally, Ori regulates oxidative stress by modulating the NRF2/HO-1/NQO-1 and AKT/AMPK-α1/GSK-3β signaling pathways
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