Span Identification of Epistemic Stance-Taking in Academic Written English

Responding to the increasing need for automated writing evaluation (AWE) systems to assess language use beyond lexis and grammar (Burstein et al., 2016), we introduce a new approach to identify rhetorical features of stance in academic English writing. Drawing on the discourse-analytic framework of engagement in the Appraisal analysis (Martin & White, 2005), we manually annotated 4,688 sentences (126,411 tokens) for eight rhetorical stance categories (e.g., PROCLAIM, ATTRIBUTION) and additional discourse elements. We then report an experiment to train machine learning models to identify and categorize the spans of these stance expressions. The best-performing model (RoBERTa + LSTM) achieved macro-averaged F1 of .7208 in the span identification of stance-taking expressions, slightly outperforming the intercoder reliability estimates before adjudication (F1 = .6629).Comment: The 18th Workshop on Innovative Use of NLP for Building Educational Application

A four-dimensional organoid system to visualize cancer cell vascular invasion

Yanagisawa, K.; Konno, M.; Liu, H.; Irie, S.; Mizushima, T.; Mori, M.; Doki, Y.; Eguchi, H.; Matsusaki, M.; Ishii, H. A Four-Dimensional Organoid System to Visualize Cancer Cell Vascular Invasion. Biology 2020, 9, 361

Cell Stress Induced Stressome Release Including Damaged Membrane Vesicles and Extracellular HSP90 by Prostate Cancer Cells

Tumor cells exhibit therapeutic stress resistance-associated secretory phenotype involving extracellular vesicles (EVs) such as oncosomes and heat shock proteins (HSPs). Such a secretory phenotype occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as a soluble form known as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in the release of EV proteins including CD9 and epithelial-to-mesenchymal transition (EMT), a key event in tumor progression. EVs derived from CRPC cells promoted EMT in normal prostate epithelial cells. Some HSP family members and their potential receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein types found by mass spectrometry. The small EVs (30-200 nm in size) were released even in a non-heated condition from the prostate cancer cells, whereas the EMT-coupled release of EVs (200-500 nm) and damaged membrane vesicles with associated HSP90 alpha was increased after heat shock stress (HSS). GAPDH and lactate dehydrogenase, a marker of membrane leakage/damage, were also found in conditioned media upon HSS. During this stress response, the intracellular chaperone CDC37 was transcriptionally induced by heat shock factor 1 (HSF1), which activated the CDC37 core promoter, containing an interspecies conserved heat shock element. In contrast, knockdown of CDC37 decreased EMT-coupled release of CD9-containing vesicles. Triple siRNA targeting CDC37, HSP90 alpha, and HSP90 beta was required for efficient reduction of this chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, we define "stressome" as cellular stress-induced all secretion products, including EVs (200-500 nm), membrane-damaged vesicles and remnants, and extracellular HSP90 and GAPDH. Our data also indicated that CDC37 is crucial for the release of vesicular proteins and tumor progression in prostate cancer

Mechanism of robust circadian oscillation of KaiC phosphorylation in vitro

By incubating the mixture of three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro, Kondo and his colleagues reconstituted the robust circadian rhythm of the phosphorylation level of KaiC (Science, 308; 414-415 (2005)). This finding indicates that protein-protein interactions and the associated hydrolysis of ATP suffice to generate the circadian rhythm. Several theoretical models have been proposed to explain the rhythm generated in this "protein-only" system, but the clear criterion to discern different possible mechanisms was not known. In this paper, we discuss a model based on the two basic assumptions: The assumption of the allosteric transition of a KaiC hexamer and the assumption of the monomer exchange between KaiC hexamers. The model shows a stable rhythmic oscillation of the phosphorylation level of KaiC, which is robust against changes in concentration of Kai proteins. We show that this robustness gives a clue to distinguish different possible mechanisms. We also discuss the robustness of oscillation against the change in the system size. Behaviors of the system with the cellular or subcellular size should shed light on the role of the protein-protein interactions in in vivo circadian oscillation