113 research outputs found

    Fuzzy automata as coalgebras

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    The coalgebraic method is of great significance to research in process algebra, modal logic, object-oriented design and component-based software engineering. In recent years, fuzzy control has been widely used in many fields, such as handwriting recognition and the control of robots or air conditioners. It is then an interesting topic to analyze the behavior of fuzzy automata from a coalgebraic point of view. This paper models different types of fuzzy automata as coalgebras with a monad structure capturing fuzzy behavior. Based on the coalgebraic models, we can define a notion of fuzzy language and consider several versions of bisimulation for fuzzy automata. A group of combinators is defined to compose fuzzy automata of two branches: state transition and output function. A case study illustrates the coalgebraic models proposed and their composition.This work has been supported by the Guangdong Science and Technology Department (Grant No. 2018B010107004) and the National Natural Science Foundation of China under grant No. 61772038, 61532019 and 61272160. L.S.B. was supported by the ERDF—European Regional Development Fund through the Operational Programme for Competitiveness and InternationalisationCOMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT, within project KLEE - POCI-01-0145-FEDER-030947

    (7R,8S,9S,12S)-1-(4-Chloro­benz­yloxy)-13,14-didehydro-12-hy­droxy-2,13-dimeth­oxy-N-methyl­morphinane

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    The title compound, C26H30ClNO4, a sinomenine derivative, has five six-membered rings, two of which are aromatic, with a dihedral angle of 34.13 (20)° between these. The N-containing ring and the fourth ring exhibit chair conformations, while the fifth ring approximates an envelope conformation. A single inter­molecular O—H⋯N hydrogen-bonding inter­action gives a one-dimensional chain structure which extends along the a axis. The absolute configuration for the mol­ecule has been determined

    (7R,8S,9S,12S)-1-Benz­yloxy-13,14-didehydro-12-hy­droxy-2,13-dimeth­oxy-N-methyl­morphinane

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    In the title compound, C26H31NO4, a sinomenine derivative, the angle between the two aromatic rings is 53.34 (4)°. The N-containing ring is in a chair conformation, while the other two non-planar rings are in a half-boat conformation. In the crystal, mol­ecules are linked by O—H⋯N inter­actions into a C(8) chain along [100]

    Mantle Flow and Olivine Fabric Transition in the Myanmar Continental Subduction Zone

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    One of the Major Advances in Mineral Physics and Seismology is the Realization that Different Olivine Fabric Types Are Functions of Temperature, Shear Stress, and Water Content in Oceanic Subducting Systems. the Distribution of Different Olivine Fabric Types and Geodynamic Processes in the Mantle Wedge above a Subducting Continental Slab Remain Poorly Understood. Here, based on Splitting Analysis of Shear Waves Recorded by 46 Stations Recently Deployed in Central Myanmar, We Reveal Trench-Perpendicular Fast Orientations between the 80 and 100 Km Slab Contours Sandwiched between Trench-Parallel Fast Orientations from the Mantle Wedge Tip to the Backarc. the Dramatic Change in Fast Orientations Indicates the Transition of Olivine Fabric Types in the Mantle Wedge Combined with Corner Flow. Cold Continental Sub-Duction and Shear Stress Reduction Caused by Partial Melting Favor B-Type and C- or E-Type Olivine Fabrics, Respectively

    Impacts of MicroRNA Gene Polymorphisms on the Susceptibility of Environmental Factors Leading to Carcinogenesis in Oral Cancer

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    BACKGROUND: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60). CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese

    Barrier-to-Autointegration Factor Proteome Reveals Chromatin-Regulatory Partners

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    Nuclear lamin filaments and associated proteins form a nucleoskeletal (“lamina”) network required for transcription, replication, chromatin organization and epigenetic regulation in metazoans. Lamina defects cause human disease (“laminopathies”) and are linked to aging. Barrier-to-autointegration factor (BAF) is a mobile and essential component of the nuclear lamina that binds directly to histones, lamins and LEM-domain proteins, including the inner nuclear membrane protein emerin, and has roles in chromatin structure, mitosis and gene regulation. To understand BAF's mechanisms of action, BAF associated proteins were affinity-purified from HeLa cell nuclear lysates using BAF-conjugated beads, and identified by tandem mass spectrometry or independently identified and quantified using the iTRAQ method. We recovered A- and B-type lamins and core histones, all known to bind BAF directly, plus four human transcription factors (Requiem, NonO, p15, LEDGF), disease-linked proteins (e.g., Huntingtin, Treacle) and several proteins and enzymes that regulate chromatin. Association with endogenous BAF was independently validated by co-immunoprecipitation from HeLa cells for seven candidates including Requiem, poly(ADP-ribose) polymerase 1 (PARP1), retinoblastoma binding protein 4 (RBBP4), damage-specific DNA binding protein 1 (DDB1) and DDB2. Interestingly, endogenous BAF and emerin each associated with DDB2 and CUL4A in a UV- and time-dependent manner, suggesting BAF and emerin have dynamic roles in genome integrity and might help couple DNA damage responses to the nuclear lamina network. We conclude this proteome is a rich source of candidate partners for BAF and potentially also A- and B-type lamins, which may reveal how chromatin regulation and genome integrity are linked to nuclear structure

    DOCK2 is involved in the host genetics and biology of severe COVID-19

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    「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target
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