2,156 research outputs found

    Extracellular Matrix Protein Tenascin C Increases Phagocytosis Mediated by CD47 Loss of Function in Glioblastoma.

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    Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of the brain tumor microenvironment (TME). CD47 has been shown to mediate immune evasion, as the CD47-SIRPα axis prevents phagocytosis of tumor cells by macrophages and other myeloid cells. In this study, we established CD47 homozygous deletion (CD47-/-) in human and mouse GBM cells and investigated the impact of eliminating the "don't eat me" signal on tumor growth and tumor-TME interactions. CD47 knockout (KO) did not significantly alter tumor cell proliferation in vitro but significantly increased phagocytosis of tumor cells by macrophages in cocultures. Compared with CD47 wild-type xenografts, orthotopic xenografts derived from CD47-/- tumor cells grew significantly slower with enhanced tumor cell phagocytosis and increased recruitment of M2-like tumor-associated microglia/macrophages (TAM). CD47 KO increased tumor-associated extracellular matrix protein tenascin C (TNC) in xenografts, which was further examined in vitro. CD47 loss of function upregulated TNC expression in tumor cells via a Notch pathway-mediated mechanism. Depletion of TNC in tumor cells enhanced the growth of CD47-/- xenografts in vivo and decreased the number of TAM. TNC knockdown also inhibited phagocytosis of CD47-/- tumor cells in cocultures. Furthermore, TNC stimulated release of proinflammatory factors including TNFα via a Toll-like receptor 4 and STAT3-dependent mechanism in human macrophage cells. These results reveal a vital role for TNC in immunomodulation in brain tumor biology and demonstrate the prominence of the TME extracellular matrix in affecting the antitumor function of brain innate immune cells. SIGNIFICANCE: These findings link TNC to CD47-driven phagocytosis and demonstrate that TNC affects the antitumor function of brain TAM, facilitating the development of novel innate immune system-based therapies for brain tumors

    4-Bromo-1-[2,6-dichloro-4-(trifluoro­meth­yl)phen­yl]-5-(4-nitro­benzyl­idene­amino)-1H-pyrazole-3-carbonitrile

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    The title compound, C18H7BrCl2F3N5O2, is an L-shaped tricyclic imine. The pyrazole ring is essentially coplanar with the nitro-substituted benzene ring [dihedral angle = 3.6 (2)°] and approximately perpendicular to the trifluoro­methyl­substituted ring [dihedral angle = 88.5 (2)°]

    Towards Realizing the Value of Labeled Target Samples: a Two-Stage Approach for Semi-Supervised Domain Adaptation

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    Semi-Supervised Domain Adaptation (SSDA) is a recently emerging research topic that extends from the widely-investigated Unsupervised Domain Adaptation (UDA) by further having a few target samples labeled, i.e., the model is trained with labeled source samples, unlabeled target samples as well as a few labeled target samples. Compared with UDA, the key to SSDA lies how to most effectively utilize the few labeled target samples. Existing SSDA approaches simply merge the few precious labeled target samples into vast labeled source samples or further align them, which dilutes the value of labeled target samples and thus still obtains a biased model. To remedy this, in this paper, we propose to decouple SSDA as an UDA problem and a semi-supervised learning problem where we first learn an UDA model using labeled source and unlabeled target samples and then adapt the learned UDA model in a semi-supervised way using labeled and unlabeled target samples. By utilizing the labeled source samples and target samples separately, the bias problem can be well mitigated. We further propose a consistency learning based mean teacher model to effectively adapt the learned UDA model using labeled and unlabeled target samples. Experiments show our approach outperforms existing methods

    Data Envelopment Analysis for Relative Efficiency Measurement of Chinese Hospitals: A Systematic Review

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    The purpose was to explore the gap between China and the international world in efficiency measurement of hospitals with Data Envelopment Analysis, and to improve the standardization of healthcare efficiency measurement in China. A systematic review was conducted using appropriate search strategies. Studies were included containing DEA approaches regarding general hospital efficiency, published in international literature and in both Chinese and English about Chinese hospitals from January 2004 to October 2014. The results showed that statistical significances were found in indicators such as number of DMUs, percentage of allocative efficiency studies, ratio of studies with multiple years, number of studies with monetary indicators in input and output sets, etc. The statistical insignificance in some indicators such as the number of input and output indicators were also found among China, Europe, USA and others. Some problems were found in current DEA-based hospital efficiency studies in China, such as inappropriate selection of input-output indicators, no bias-correction on efficiency scores, etc. The standardization of DEA methods applied in China’s hospital efficiency research needs to be improved. Chinese researchers should pay more attention to latest international research findings, so as to keep pace with the cutting edge hospital efficiency research

    4-Bromo-1-[2,6-dichloro-4-(trifluoro­meth­yl)phen­yl]-5-(4-methoxy­benzyl­ideneamino)-1H-pyrazole-3-carbonitrile

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    The title compound, C19H10BrCl2F3N4O, is an imine with an overall Y shape. The dihedral angles between the pyrazole ring and the methoxy- and trifluoromethyl-substituted benzene ring planes are 88.4 (2) and 65.8 (2)°, respectively

    Investigation on Fitting Method of Snail Structural Lines

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    For the current status of the spudcan design and combining the characteristics of bionics, on the basis of shells on the solid model, the paper study the spiral geometry characteristics and distribution. Regarding the shape of the surface characteristics of the spiral portion and snail shells spiral suture lines, a feature reverse scan statistics can be made. Snail shells overall shape evaluation can be established and micro-element methods are used to deduce the 2D mathematical expression so as to provide a good reference for the design of jack-up platform spudcan
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