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1. chinaXiv:202010.00061 [pdf]

基于span分类模型的医学概念抽取方法

汤勇韬; 余杰; 李莎莎; 纪斌; 谭郁松; 吴庆波
Subjects: Computer Science >> Natural Language Understanding and Machine Translation

最近,如何构造电子病历(EMR)引起了研究人员的极大关注。从EMR中提取临床概念是EMR结构化的关键部分。临床概念提取的性能将直接影响与EMR结构化相关的下游任务的性能。但是,主流方法中,序列标记模型有一些缺点。基于序列标记的临床概念提取方法不符合人类的语言认知模型。同时,这种方法产生的提取结果很难与下游任务耦合,这将导致错误传播并影响下游任务的性能。为了解决这些问题,我们提出了一种基于span分类的方法,通过考虑字符序列的整体语义而不是每个字符的语义来提高临床概念提取任务的性能。我们将此模型称为span分类模型。实验表明,span分类模型在2012年i2b2 NLP挑战赛的语料库中获得了最佳的微观平均F1得分(81.22%),并获得了与2010年i2b2 NLP挑战赛的SOTA相当的F1得分(89.25%)。此外,我们的方法的性能始终优于序列标记模型,例如BiLSTM-CRF模型和softmax分类器。

submitted time 2020-10-27 Hits10046Downloads988 Comment 0

2. chinaXiv:201605.01461 [pdf]

Guidelines for monitoring autophagy in Caenorhabditis elegans

Zhang, Hong; Guo, Bin; Lin, Long; Lu, Qun; Wu, Fan; Chang, Jessica T.; Hansen, Malene; Kumsta, Caroline; Lapierre, Louis R.; Jia, Kailiang; Kovacs, Attila L.; Legouis, Renaud; Melendez, Alicia; Melendez, Alicia; O'Rourke, Eyleen J.; Sato, Ken; Sato, Miyuki; Wang, Xiaochen
Subjects: Biology >> Biophysics >> Cell Biology

The cellular recycling process of autophagy has been extensively characterized with standard assays in yeast and mammalian cell lines. In multicellular organisms, numerous external and internal factors differentially affect autophagy activity in specific cell types throughout the stages of organismal ontogeny, adding complexity to the analysis of autophagy in these metazoans. Here we summarize currently available assays for monitoring the autophagic process in the nematode C. elegans. A combination of measuring levels of the lipidated Atg8 ortholog LGG-1, degradation of well-characterized autophagic substrates such as germline P granule components and the SQSTM1/p62 ortholog SQST-1, expression of autophagic genes and electron microscopy analysis of autophagic structures are presently the most informative, yet steady-state, approaches available to assess autophagy levels in C. elegans. We also review how altered autophagy activity affects a variety of biological processes in C. elegans such as L1 survival under starvation conditions, dauer formation, aging, and cell death, as well as neuronal cell specification. Taken together, C. elegans is emerging as a powerful model organism to monitor autophagy while evaluating important physiological roles for autophagy in key developmental events as well as during adulthood.

submitted time 2016-05-12 Hits2374Downloads1492 Comment 0

3. chinaXiv:201605.01421 [pdf]

The Effect of Ionizing Radiation on mRNA Levels of the DNA Damage Response Genes Rad9, Rad1 and Hus1 in Various Mouse Tissues

Zhang, Zhenya; Li, Kaiming; Cai, Zeyuan; Fang, Yu; An, Lili; Hu, Zhishang; Hang, Haiying; Cai, Zeyuan; Hu, Zhishang
Subjects: Biology >> Biophysics >> Biology

Rad9, Rad1 and Hus1 are essential genes conserved from yeast to humans. They form a heterotrimer complex (9-1-1 complex) that participates in the cell cycle checkpoint activation and DNA damage repair in eukaryotic cells. Rad9, Rad1 and Hus1 deficient cells are hypersensitive to ionizing radiation and mouse cells deleted for anyone of the three genes are highly sensitive to the killing by gamma rays. We propose that ionizing radiation-induced transcription of these genes is a mechanism by which cells respond to radiation-induced damage. In this study we used quantitative real-time RT-PCR(qPCR) to analyze the mRNA levels of Rad9, Rad1 and Hus1 in various tissues isolated from mice that were either mock irradiated or exposed to 10 Gy gamma radiation. Our results indicated that the mRNA levels of Rad9, Rad1 and Hus1 genes were very different among these tissues, and we found high natural levels of mRNA in the spleen, lung, ovary and testis of mice before exposure to radiation. The mRNA levels of the three genes were well correlated across these tissues, being high, medium or low in each of the tissues simultaneously. The mRNA levels of the three genes were analyzed at 2, 6, 12, 24 and 48 h after irradiation. In most tissues Rad9 was strongly induced at 2 and 12 h time points and Hus1 was strongly induced at 2, 12 and 48 h time points, but Rad1 was minimally induced in most of the tissues with the exception of slightly higher levels in the heart and lung tissues at the 48 h time point. These results suggest that the regulation mechanisms for the mRNA levels of the three genes in response to ionizing radiation are complex and not well orchestrated. We also detected the induction of Rad9 and Hus1 proteins in the heart and liver of the animals after irradiation, and found that Rad9 protein levels were highly induced in both the heart and liver, while the Hus1 protein levels were significantly induced only in the liver, suggesting that Rad9 and Hus1 protein levels are not regulated in a coordinated manner in response to irradiation. We then went on to measure the mRNA levels of the three genes and the Rad9 and Hus1 protein levels in the mouse liver cell line (NCTC 1469) in response to irradiation in vitro. All three genes in the cultured cells were minimally induced at mRNA level, obviously different from the highly dynamic induction in liver. Rad9 and Hus1 were significantly induced at the protein level, but the induced Rad9 protein levels were higher than the Hus1 levels. Taken together, the good correlation of the mRNA levels of Rad9, Hus1 and Rad1 genes across different tissues isolated from the animals that were mock irradiated and the lack of correlation in mRNA as well as protein levels after irradiation suggest that the 9-1-1 complex has evolved to play various physiological roles in tissues rather than dealing with high doses of gamma radiation or other genotoxic agents. (C) 2015 by Radiation Research Society

submitted time 2016-05-12 Hits2673Downloads1407 Comment 0

4. chinaXiv:201605.01345 [pdf]

Structure and Catalytic Mechanisms of Histone Deacetylases

Cao Duan-Fang; Yang Na
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Lysine acetylation is one of the most widely studied post-translational modifications of histones. It plays important roles in the regulation of chromatin remodeling and gene expression. This modification is dynamically regulated in vivo by histone acetyltransferases and deacetylases. Besides histone substrates, many histone deacetylases can also catalyze deacetylation of non-histone substrates, and participate in the regulation of various biological pathways. In this review, we discuss the classification, structure, function, and catalytic mechanisms of the four known classes of human histone deacetylases, as well as the progress in the development and application of small molecule inhibitors and activators of these deacetylases.

submitted time 2016-05-11 Hits1894Downloads1472 Comment 0

5. chinaXiv:201605.01297 [pdf]

Asymmetric dimethylarginine exacerbates A beta-induced toxicity and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease

Luo, Yunfeng; Yue, Wenhui; Quan, Xin; Wang, Yue; Lu, Zhongbing; Zhao, Baolu
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Growing evidence suggests a strong association between cardiovascular risk factors and incidence of Alzheimer disease (AD). Asymmetric dimethylarginine (ADMA), the endogenous nitric oxide synthase inhibitor, has been identified as an independent cardiovascular risk factor and is also increased in plasma of patients with AD. However, whether ADMA is involved in the pathogenesis of AD is unknown. In this study, we found that ADMA content was increased in a transgenic Caenorhabditis elegans beta-amyloid (A beta) overexpression model, strain CL2006, and in human SH-SY5Y cells overexpressing the Swedish mutant form of human A beta precursor protein (APPsw). Moreover, ADMA treatment exacerbated A beta-induced paralysis and oxidative stress in CL2006 worms and further elevated oxidative stress and A beta secretion in APPsw cells. Knockdown of type 1 protein arginine N-methyltransferase to reduce ADMA production failed to show a protective effect against A beta toxicity, but resulted in more paralysis in CL2006 worms as well as increased oxidative stress and A beta secretion in APPsw cells. However, overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) to promote ADMA degradation significantly attenuated oxidative stress and A beta secretion in APPsw cells. Collectively, our data support the hypothesis that elevated ADMA contributes to the pathogenesis of AD. Our findings suggest that strategies to increase DDAH1 activity in neuronal cells may be a novel approach to attenuating AD development. (C) 2014 Elsevier Inc. All rights reserved.

submitted time 2016-05-11 Hits1789Downloads1006 Comment 0

6. chinaXiv:201605.00745 [pdf]

FoxO1-mediated autophagy is required for NK cell development and innate immunity

Wang, Shuo; Xia, Pengyan; Huang, Guanling; Zhu, Pingping; Liu, Jing; Ye, Buqing; Du, Ying; Fan, Zusen;
Subjects: Biology >> Biophysics

Natural killer (NK) cells exert a crucial role in early immune responses as a major innate effector component. However, the underlying mechanisms of NK cell development remain largely elusive. Here we show that robust autophagy appears in the stage of immature NK cells (iNKs), which is required for NK cell development. Autophagy defects result in damaged mitochondria and accumulation of reactive oxygen species (ROS) that leads to apoptosis of NK cells. Autophagy protects NK cell viability during development through removal of damaged mitochondria and intracellular ROS. Phosphorylated Forkhead box O (FoxO)1 is located to the cytoplasm of iNKs and interacts with Atg7, leading to induction of autophagy. FoxO1 deficiency or an inactive FoxO1(AAA) mutant abrogates autophagy initiation in iNKs and impairs NK cell development and viral clearance. Therefore we conclude that FoxO1-mediated autophagy is required for NK cell development and NK cell-induced innate immunity.

submitted time 2016-05-05 Hits1928Downloads1110 Comment 0

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