104 research outputs found

    Will the Independent Director Institution Work in China

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    AUTOMATED FIVE-AXIS TOOL PATH GENERATION BASED ON DYNAMIC ANALYSIS

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    Ph.DDOCTOR OF PHILOSOPH

    Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

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    Nasopharyngeal carcinoma (NPC) is one of the most common malignant cancers in Southeast Asia and Southern China. Centipeda minima extract (CME) had previously demonstrated anti-cancer effects in human NPC. Brevilin A, a sesquiterpene lactone isolated from C. minima, has been reported to exhibit biological activities. In this study, we investigated its anti-NPC effect and further explored its molecular mechanisms. The effects of brevilin A were tested in the NPC cell lines CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. Effects of brevilin A on cell viability were determined by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. The molecular mechanism of cell cycle regulation and apoptosis were investigated via Western blot. Results showed that brevilin A inhibited NPC cell viability in a concentration- and time-dependent manner. Brevilin A induced cell cycle arrest at G2/M and induced apoptosis. Western blot results demonstrated that brevilin A could down-regulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, while up-regulating cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by brevilin A showed dynamic changes according to dose and time. In the tumor xenograft model, brevilin A could reduce tumor growth, at a similar magnitude to cisplatin. However, notably, whereas cisplatin treatment led to significant weight loss in treated mice, treatment with brevilin A did not, indicating its relative lack of toxicity. Taken together, brevilin A regulated cell cycle, activated the caspase signaling pathway, and inhibited PI3K/AKT/mTOR and STAT3 signaling pathways in vitro, and exhibited similar efficacy to the common chemotherapeutic cisplatin in vivo, without its associated toxicity. These findings provide a framework for the preclinical development of brevilin A as a chemotherapeutic for NPC

    CHD-CXR: a de-identified publicly available dataset of chest x-ray for congenital heart disease

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    Congenital heart disease is a prevalent birth defect, accounting for approximately one-third of major birth defects. The challenge lies in early detection, especially in underdeveloped medical regions where a shortage of specialized physicians often leads to oversight. While standardized chest x-rays can assist in diagnosis and treatment, their effectiveness is limited by subtle cardiac manifestations. However, the emergence of deep learning in computer vision has paved the way for detecting subtle changes in chest x-rays, such as lung vessel density, enabling the detection of congenital heart disease in children. This highlights the need for further investigation. The lack of expert-annotated, high-quality medical image datasets hinders the progress of medical image artificial intelligence. In response, we have released a dataset containing 828 DICOM chest x-ray files from children with diagnosed congenital heart disease, alongside corresponding cardiac ultrasound reports. This dataset emphasizes complex structural characteristics, facilitating the transition from machine learning to machine teaching in deep learning. To ascertain the dataset's applicability, we trained a preliminary model and achieved an area under the receiver operating characteristic curve (ROC 0.85). We provide detailed introductions and publicly available datasets at: https://www.kaggle.com/competitions/congenital-heart-disease

    Insertion of an Esterase Gene into a Specific Locust Pathogen (Metarhizium acridum) Enables It to Infect Caterpillars

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    An enduring theme in pathogenic microbiology is poor understanding of the mechanisms of host specificity. Metarhizium is a cosmopolitan genus of invertebrate pathogens that contains generalist species with broad host ranges such as M. robertsii (formerly known as M. anisopliae var. anisopliae) as well as specialists such as the acridid-specific grasshopper pathogen M. acridum. During growth on caterpillar (Manduca sexta) cuticle, M. robertsii up-regulates a gene (Mest1) that is absent in M. acridum and most other fungi. Disrupting M. robertsii Mest1 reduced virulence and overexpression increased virulence to caterpillars (Galleria mellonella and M. sexta), while virulence to grasshoppers (Melanoplus femurrubrum) was unaffected. When Mest1 was transferred to M. acridum under control of its native M. robertsii promoter, the transformants killed and colonized caterpillars in a similar fashion to M. robertsii. MEST1 localized exclusively to lipid droplets in M. robertsii conidia and infection structures was up-regulated during nutrient deprivation and had esterase activity against lipids with short chain fatty acids. The mobilization of stored lipids was delayed in the Mest1 disruptant mutant. Overall, our results suggest that expression of Mest1 allows rapid hydrolysis of stored lipids, and promotes germination and infection structure formation by M. robertsii during nutrient deprivation and invasion, while Mest1 expression in M. acridum broadens its host range by bypassing the regulatory signals found on natural hosts that trigger the mobilization of endogenous nutrient reserves. This study suggests that speciation in an insect pathogen could potentially be driven by host shifts resulting from changes in a single gene

    Analysis and Prediction of Translation Rate Based on Sequence and Functional Features of the mRNA

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    Protein concentrations depend not only on the mRNA level, but also on the translation rate and the degradation rate. Prediction of mRNA's translation rate would provide valuable information for in-depth understanding of the translation mechanism and dynamic proteome. In this study, we developed a new computational model to predict the translation rate, featured by (1) integrating various sequence-derived and functional features, (2) applying the maximum relevance & minimum redundancy method and incremental feature selection to select features to optimize the prediction model, and (3) being able to predict the translation rate of RNA into high or low translation rate category. The prediction accuracies under rich and starvation condition were 68.8% and 70.0%, respectively, evaluated by jackknife cross-validation. It was found that the following features were correlated with translation rate: codon usage frequency, some gene ontology enrichment scores, number of RNA binding proteins known to bind its mRNA product, coding sequence length, protein abundance and 5′UTR free energy. These findings might provide useful information for understanding the mechanisms of translation and dynamic proteome. Our translation rate prediction model might become a high throughput tool for annotating the translation rate of mRNAs in large-scale

    The Determinants of Corporate Social Responsibility Disclosure: The Case of Malaysian Government-Linked Companies in Malaysia

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    The implementation of Government-Linked Company (GLC) Transformation Program 2005/06 by government is one effort to promote Corporate Social Responsibility (CSR) disclosures among its government-linked companies (GLCs). CSR issues are being stressed in the Silver Book included in the GLC Transformation Manual under the GLC Transformation Program 2005/06. It is questionable as to whether the introduction of the Silver Book really reflects goods prospects for government-linked companies to disclose their CSR, and whether there are any other factors that will influence the GLCs in Malaysia to disclose their CSR. Thus, the objective of this study is to examine whether the introduction of the Silver Book affect the CSR disclosure among Malaysian GLCs as well as to examine the determinants of CSR disclosure, focusing on the profitability, board size and board independence. Multiple linear regression analysis is being used to examine the relationship between all the independent variables and dependent variable. Findings show that there is an increasing trend in CSR disclosure among Malaysian GLCs from year 2011 until 2015. Two variables i.e. board size and board independence has been found to have a significant positive relationship with the CSR disclosure. This study gives implications to various parties such as Malaysian Government, Bursa Malaysia, Security Commission and other relevant parties in to improve CSR awareness, practices, disclosures and quality in GLCs

    Genome Sequencing and Comparative Transcriptomics of the Model Entomopathogenic Fungi Metarhizium anisopliae and M. acridum

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    Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ∼30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ∼16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogenous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties
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